marketing fragment 8.5 x 12

Endothelial Biomedicine

The endothelium, the cell layer that forms the inner liningof blood vessels, is a spatially distributed system that extendsto all reaches of the human body. Today, clinical and basicresearch demonstrates that the endothelium plays a crucialrole in mediating homeostasis and is involved in virtuallyevery disease, either as a primary determinant of pathophysio-logy or as a victim of collateral damage. Indeed, the endothe-lium has remarkable, though largely untapped, diagnostic andtherapeutic potential. This volume endeavors to bridge thebench-to-bedside gap in endothelial biomedicine, with thegoal of advancing research and development and improvinghuman health. The book is the first to systematically inte-grate knowledge about the endothelium from different organ-specific disciplines, including neurology, pulmonary, cardio-logy, gastroenterology, rheumatology, infectious disease,hematology-oncology, nephrology, and dermatology. More-over, it is unique in its interdisciplinary approach, drawingon expertise from such diverse fields as evolutionary biology,comparative biology, molecular and cell biology, mathemat-ical modeling and complexity theory, translational research,and clinical medicine.

Dr. William C. Aird received his medical degree from theUniversity of Western Ontario in 1985. After completing hisinternal medicine and chief medical residency at the Univer-sity of Toronto, he undertook a Hematology fellowship at theBrigham and Women’s Hospital, Harvard Medical School. Dr.Aird received his postdoctoral training in the Departmentof Biology at the Massachusetts Institute of Technology. In1996, he established an independent research program in theDivision of Molecular Medicine at the Beth Israel DeaconessMedical Center. Dr. Aird is currently Associate Professor ofMedicine at Harvard Medical School and Chief of the Divisionof Molecular and Vascular Medicine, at Beth Israel DeaconessMedical Center, Boston, Massachusetts.

© Cambridge University Press www.cambridge.org

Cambridge University Press978-0-521-85376-7 - Endothelial BiomedicineEdited by William C. Aird M. D.FrontmatterMore information

http://www.cambridge.org/0521853761

http://www.cambridge.org


Endothelial Biomedicine

Edited by

William C. Aird M.D.Chief, Division of Molecular and Vascular Medicine

Beth Israel Deaconess Medical CenterAssociate Professor of Medicine

Harvard Medical School






CAMBRIDGE UNIVERSITY PRESS

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Endothelial biomedicine / edited by William C. Aird.p.; cm.

Includes bibliographical references and index.

ISBN 978-0-521-85376-7 (hardcover)1. Endothelium. I. Aird, William C.

[DNLM: 1. Endothelium – physiology. 2. EndothelialCells – physiology. 3. Endothelium – physiopathology. QS 532.5.E7 E561 2007] I. Title.

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v

To my wife Renee, and children Xan, Ali, and Jamie






Contents

Editor, Associate Editors, Artistic Consultant,and Contributors page xxi

Preface xxxix

PA RT I : C O N T E X T

History of Medicine

1. The Endothelium in History 5Manfred D. Laubichler, William C. Aird, andJane Maienshein

Evolution, Comparative Biology, and Development

2. Introductory Essay: Evolution, ComparativeBiology, and Development 23William C. Aird and Manfred D. Laubichler

3. Evolution of Cardiovascular Systems and TheirEndothelial Linings 29Warren W. Burggren and Carl L. Reiber

4. The Evolution and Comparative Biology of VascularDevelopment and the Endothelium 50J. Douglas Coffin

5. Fish Endothelium 59Kenneth R. Olson

6. Hagfish: A Model for Early Endothelium 66Pavan K. Cheruvu, Daniel Gale, Ann M. Dvorak,David Haig, and William C. Aird

7. The Unusual Cardiovascular System of theHemoglobinless Antarctic Icefish 74H. William Detrich III

8. The Fish Endocardium: A Review on the TeleostHeart 79Jose M. Icardo

9. Skin Breathing in Amphibians 85Glenn J. Tattersall

vii






viii C O N T E N T S

10. Avian Endothelium 92Thomas J. Poole

11. Spontaneous Cardiovascular and EndothelialDisorders in Dogs and Cats 94John E. Rush

12. Giraffe Cardiovascular Adaptations to Gravity 99Alan R. Hargens, Knut Pettersson, andRonald W. Millard

13. Energy Turnover and Oxygen Transport in theSmallest Mammal: The Etruscan Shrew 107Klaus D. Jurgens

14. Molecular Phylogeny 113John H. McVey

15. Darwinian Medicine: What EvolutionaryMedicine Offers to Endothelium Researchers 122Randolf M. Nesse and Alan Weder

16. The Ancestral Biomedical Environment 129S. Boyd Eaton, Loren Cordain, and AnthonySebastian

17. Putting Up Resistance: Maternal–Fetal Conflictover the Control of Uteroplacental Blood Flow 135David Haig

18. Xenopus as a Model to Study EndothelialDevelopment and Modulation 142Aldo Ciau-Uitz, Claire Fernandez, andRoger Patient

19. Vascular Development in Zebrafish 150Sameer S. Chopra and Tao P. Zhong

20. Endothelial Cell Differentiation and VascularDevelopment in Mammals 161Cam Patterson

21. Fate Mapping 167Takashi Mikawa

22. Pancreas and Liver: Mutual Signaling duringVascularized Tissue Formation 173Eckhard Lammert

23. Pulmonary Vascular Development 181Peter Lloyd Jones

Metaphors

24. Shall I Compare the Endothelium to a Summer’sDay: The Role of Metaphor in CommunicatingScience 199Steven Moskowitz and William C. Aird

25. The Membrane Metaphor: Urban Design and theEndothelium 211Kenneth L. Kaplan and Daniel L. Schodek






C O N T E N T S ix

26. Computer Metaphors for the Endothelium 215Dexter Pratt

PA RT I I : E N D OT H E L IA L C E L L A S I N P U T- O U T P U TD E V I C E

Input

27. Introductory Essay: Endothelial Cell Input 227Helmut G. Augustin

28. Hemodynamics in the Determination ofEndothelial Phenotype and FlowMechanotransduction 230Peter F. Davies

29. Hypoxia-Inducible Factor 1 246Gregg L. Semenza

30. Integrative Physiology of Endothelial Cells:Impact of Regional Metabolism on theComposition of Blood-Bathing Endothelial Cells 256Mitchell L. Halperin and Kamel S. Kamel

31. Tumor Necrosis Factor 261Jordan S. Pober

32. Vascular Permeability Factor/Vascular EndothelialGrowth Factor and Its Receptors: EvolvingParadigms in Vascular Biology and Cell Signaling 266Debarata Mukhopadhyay, Resham Bhattacharya,and Deborah A. Hughes

33. Function of Hepatocyte Growth Factor and ItsReceptor c-Met in Endothelial Cells 285Xue Wang, Augustine M.K. Choi, andStefan W. Ryter

34. Fibroblast Growth Factors 291Masahiro Murakami, Arye Elfenbein, and MichaelSimons

35. Transforming Growth Factor-β and theEndothelium 304Barbara J. Ballermann

36. Thrombospondins 324Sareh Parangi and Jack Lawler

37. Neuropilins: Receptors Central to Angiogenesisand Neuronal Guidance 337Diane Bielenberg, Peter Kurschat, and MichaelKlagsbrun

38. Vascular Functions of Eph Receptors and EphrinLigands 345Helmut G. Augustin

39. Endothelial Input from the Tie1 and Tie2Signaling Pathway 352Daniel Dumont






x C O N T E N T S

40. Slits and Netrins in Vascular Patterning: TakingCues from the Nervous System 360Kye Won Park, Lisa D. Urness, and Dean Y. Li

41. Notch Genes: Orchestrating EndothelialDifferentiation 368Yasuhiro Funahashi, Carrie J. Shawber, andJan Kitajewski

42. Reactive Oxygen Species 375Kaikobad Irani

43. Extracellular Nucleotides and Nucleosides asAutocrine and Paracrine Regulators within theVasculature 384Silvia Deaglio and Simon C. Robson

44. Syndecans 396Eugene Tkachenko, John M. Rhodes, andMichael Simons

45. Sphingolipids and the Endothelium 403Timothy Hla

46. Endothelium: A Critical Detector ofLipopolysaccharide 410Jaswinder Kaur and Paul Kubes

47. Receptor for Advanced Glycation End-productsand the Endothelium: A Path to theComplications of Diabetes and Inflammation 419Jean-Luc Wautier and Ann Marie Schmidt

48. Complement 430Anne Nicholson-Weller

49. Kallikrein-Kinin System 444Robert Colman

50. Opioid Receptors in Endothelium 451Kalpna Gupta and Elliot J. Stephenson

51. Snake Toxins and Endothelium 461Jay W. Fox and Solange M.T. Serrano

52. Inflammatory Cues Controlling Lymphocyte–Endothelial Interactions in Fever-RangeThermal Stress 471Qing Chen, Kristen Clancy, Wan-Chao Wang, andSharon S. Evans

53. Hyperbaric Oxygen and Endothelial Responses inWound Healing and Ischemia-Reperfusion Injury 480Bryan Belikoff, Wende R. Reenstra, and Jon A. Buras

54. Barotrauma 489Deborah A. Quinn and Charles A. Hales

55. Endothelium and Diving 497Alf O. Brubakk, Olav S. Eftedal, and Ulrik Wisløff

56. Exercise and the Endothelium 506Ulrik Wisløff, Per M. Haram, and Alf O. Brubakk






C O N T E N T S xi

57. The Endothelium at High Altitude 516Nicholas L.M. Cruden and David J. Webb

58. Endothelium in Space 520Janice V. Meck and Ralph E. Purdy

59. Toxicology and the Endothelium 527Howard D. Beall and J. Douglas Coffin

60. Pericyte–Endothelial Interactions 536Mark W. Majesky

61. Vascular Smooth Muscle Cells: The Musclebehind Vascular Biology 545Shivalika Handa, Karolina Kolodziejska, andMansoor Husain

62. Cross-Talk between the Red Blood Cell and theEndothelium: Nitric Oxide as a Paracrine andEndocrine Regulator of Vascular Tone 562Sruti Shiva and Mark T. Gladwin

63. Leukocyte–Endothelial Cell Interactions 576Volker Vielhauer, Xavier Cullere, and TanyaMayadas

64. Platelet–Endothelial Interactions 587Patricia B. Maguire, Orina Belton, NiaobhO’Donoghue, Sandra Austin, and JudithCoppinger

65. Cardiomyocyte–Endothelial Cell Interactions 602Jian Li and Frank W. Sellke

66. Interactions between Hepatocytes and LiverSinusoidal Endothelial Cells 609David Semela and Vijay Shah

67. Stellate Cell–Endothelial Cell Interactions 616Haruki Senoo

68. Podocyte–Endothelial Interactions 620Susan E. Quaggin

Coupling

69. Introductory Essay: Endothelial Cell Coupling 629Michael Simons

70. Endothelial and Epithelial Cells: General Principlesof Selective Vectorial Transport 632Rolf Kinne

71. Electron Microscopic–Facilitated Understandingof Endothelial Cell Biology: ContributionsEstablished during the 1950s and 1960s 643Ann M. Dvorak

72. Weibel-Palade Bodies: Vesicular Trafficking onthe Vascular Highways 657Charles J. Lowenstein, Craig N. Morrell, andMunekazu Yamakuchi






xii C O N T E N T S

73. Multiple Functions and Clinical Uses of Caveolaein Endothelium 664Lucy A. Carver and Jan E. Schnitzer

74. Endothelial Structures Involved in VascularPermeability 679Radu V. Stan

75. Endothelial Luminal Glycocalyx: Protective Barrierbetween Endothelial Cells and Flowing Blood 689Bernard M. van den Berg, Max Nieuwdorp, ErikStroes, and Hans Vink

76. Endothelial Cell Cytoskeleton 696Christopher V. Carman

77. Endothelial Cell Integrins 707Joseph H. McCarty and Richard O. Hynes

78. Aquaporin Water Channels and the Endothelium 714Alan S. Verkman

79. Ion Channels in Vascular Endothelium 721Xiaoqiang Yao

80. Regulation of Angiogenesis and VascularRemodeling by Endothelial Akt Signaling 729Ichiro Shiojima and Kenneth Walsh

81. Mitogen-Activated Protein Kinases 737Natalia V. Bogatcheva and Alexander D. Verin

82. Protein Kinase C 746Alex Toker

83. Rho GTP-Binding Proteins 753Allan Murray

84. Protein Tyrosine Phosphatases 764Arne Ostman and Kai Kappert

85. Role of β-Catenin in Endothelial Cell Function 773Anna Cattelino and Stefan Liebner

86. Nuclear Factor-κB Signaling in Endothelium 784Kaiser M. Bijli and Arshad Rahman

87. Peroxisome Proliferator-Activated Receptors andthe Endothelium 796Jonathan D. Brown and Jorge Plutzky

88. GATA Transcription Factors 806Takashi Minami

89. Coupling: The Role of Ets Factors 812Peter Oettgen

90. Early Growth Response-1 Coupling in VascularEndothelium 818Levon M. Khachigian and Valerie C. Midgley

91. KLF2: A “Molecular Switch” RegulatingEndothelial Function 822Zhiyong Lin and Mukesh K. Jain






C O N T E N T S xiii

92. NFAT Transcription Factors 828Takashi Minami

93. Forkhead Signaling in the Endothelium 834Md. Ruhul Abid and William C. Aird

94. Genetics of Coronary Artery Disease andMyocardial Infarction: The MEF2 SignalingPathway in the Endothelium 847Stephen R. Archacki, Sun-Ah You, Quansheng Xi,and Qing Wang

95. Vezf1: A Transcriptional Regulator of theEndothelium 855Frank Kuhnert and Heidi Stuhlmann

96. Sox Genes: At the Heart of EndothelialTranscription 861Neville Young and Peter Koopman

97. Id Proteins and Angiogenesis 868Robert Benezra and Erik Henke

Output

98. Introductory Essay: Endothelial Cell Output 879William C. Aird

99. Proteomic Mapping of Endothelium andVascular Targeting in Vivo 881Lucy A. Carver and Jan E. Schnitzer

100. A Phage Display Perspective 898Amado J. Zurita, Wadih Arap, andRenata Pasqualini

101. Hemostasis and the Endothelium 909William C. Aird

102. Von Willebrand Factor 915Tom Diacovo

103. Tissue Factor Pathway Inhibitor 922Alan E. Mast

104. Tissue Factor Expression by the Endothelium 932Gernot Schabbauer and Nigel Mackman

105. Thrombomodulin 939Marlies Van de Wouwer and Edward M. Conway

106. Heparan Sulfate 947Nicholas W. Shworak

107. Antithrombin 960Nicholas W. Shworak

108. Protein C 973Marlies Van de Wouwer and Edward M. Conway

109. Vitamin K–Dependent Anticoagulant Protein S 982Bjorn Dahlback






xiv C O N T E N T S

110. Nitric Oxide as an Autocrine and ParacrineRegulator of Vessel Function 988William C. Sessa

111. Heme Oxygenase and Carbon Monoxide inEndothelial Cell Biology 994Hong Pyo Kim, Stefan W. Ryter, and AugustineM.K. Choi

112. Endothelial Eicosanoids 1004Kenneth K. Wu

113. Regulation of Endothelial Barrier Responses andPermeability 1015Joe G.N. Garcia

114. Molecular Mechanisms of LeukocyteTransendothelial Cell Migration 1030F. William Luscinskas

115. Functions of Platelet-Endothelial Cell AdhesionMolecule-1 in the Vascular Endothelium 1037Peter J. Newman and Debra K. Newman

116. P-Selectin 1049Rodger P. McEver

117. Intercellular Adhesion Molecule-1 and VascularCell Adhesion Molecule-1 1058Silvia Muro

118. E-Selectin 1071David Milstone

119. Endothelial Cell Apoptosis 1081Elizabeth O. Harrington, Qing Lu, andSharon Rounds

120. Endothelial Antigen Presentation 1098Andrew H. Lichtman

PA RT I I I : VA S C U L A R B E D / O RG A N S T RU C T U R EA N D F U N C T I O N I N H E A LT H A N D D I S E A S E

121. Introductory Essay: The Endothelium in Healthand Disease 1111William C. Aird

122. Hereditary Hemorrhagic Telangiectasia: A Modelto Probe the Biology of the Vascular Endothelium 1113Mourad Toporsian and Michelle Letarte

123. Blood–Brain Barrier 1124Christian Weidenfeller and Eric V. Shusta

124. Brain Endothelial Cells Bridge Neural andImmune Networks 1140Kevin J. Tracey and Christine N. Metz






C O N T E N T S xv

125. The Retina and Related Hyaloid Vasculature:Developmental and PathologicalAngiogenesis 1154Laura Benjamin

126. Microheterogeneity of Lung Endothelium 1161Troy Stevens

127. Bronchial Endothelium 1171Elizabeth Wagner and Aigul Moldobaeva

128. The Endothelium in Acute Respiratory DistressSyndrome 1178Mark L. Martinez and Guy A. Zimmerman

129. The Central Role of Endothelial Cells in SevereAngioproliferative Pulmonary Hypertension 1193Norbert F. Voelkel and Mark R. Nicolls

130. Emphysema: An Autoimmune Vascular Disease? 1199Norbert F. Voelkel and LaimuteTaraseviciene-Stewart

131. Endothelial Mechanotransduction in Lung:Ischemia in the Pulmonary Vasculature 1202Shampa Chatterjee and Aron B. Fisher

132. Endothelium and the Initiation ofAtherosclerosis 1214Myron I. Cybulsky

133. The Hepatic Sinusoidal Endothelial Cell 1226Laurie D. DeLeve

134. Hepatic Macrocirculation: Portal HypertensionAs a Disease Paradigm of Endothelial CellSignificance and Heterogeneity 1239Winston Dunn and Vijay Shah

135. Inflammatory Bowel Disease 1248Ossama A. Hatoum and David G. Binion

136. The Vascular Bed of Spleen in Health andDisease 1255Peter Balogh

137. Adipose Tissue Endothelium 1265Gary Hausman

138. Renal Endothelium 1271Bruce Molitoris

139. Uremia 1278Jan T. Kielstein and Danilo Fliser

140. The Influence of Dietary Salt Intake onEndothelial Cell Function 1287Paul W. Sanders

141. The Role of the Endothelium in SystemicInflammatory Response Syndrome and Sepsis 1294Laszlo M. Hoesel and Peter A. Ward






xvi C O N T E N T S

142. The Endothelium in Cerebral Malaria: Botha Target Cell and a Major Player 1303Valery Combes, Jin Ning Lou, and Georges E. Grau

143. Hemorrhagic Fevers: Endothelial Cells andEbola-Virus Hemorrhagic Fever 1311Tatiana A. Afanasieva, Victoria Wahl-Jensen, JochenSeebach, Herrmann Schillers, Dessy Nikova, UteStroher, Heinz Feldmann, and Hans-JoachimSchnittler

144. Effect of Smoking on Endothelial Function andCardiovascular Disease 1320Rajat S. Barua and John A. Ambrose

145. Disseminated Intravascular Coagulation 1332Marcel Levi

146. Thrombotic Microangiopathy 1337Jeffrey Laurence

147. Heparin-Induced Thrombocytopenia 1344Andreas Greinacher and Theodore E. Warkentin

148. Sickle Cell Disease Endothelial Activation andDysfunction 1352Robert P. Hebbel

149. The Role of Endothelial Cells in theAntiphospholipid Syndrome 1360Jacob H. Rand and Xiao-Xuan Wu

150. Diabetes 1370Angelika Bierhaus, Hans-Peter Hammes, andPeter P. Nawroth

151. The Role of the Endothelium in Normal andPathologic Thyroid Function 1386Jamie Mitchell, Anthony Hollenberg, and SarehParangi

152. Endothelial Dysfunction and the Link toAge-Related Vascular Disease 1397Jay M. Edelberg and May J. Reed

153. Kawasaki Disease 1405Jane C. Burns

154. Systemic Vasculitis: Autoantibodies TargetingEndothelial Cells 1411Miri Blank, Sonja Praprotnik, and YehudaShoenfeld

155. High Endothelial Venule-like Vessels in HumanChronic Inflammatory Diseases 1419Jean-Philippe Girard

156. Endothelium and Skin 1431Peter Petzelbauer, Marion Groger, Robert Loewe,and Rainer Kunstfeld

157. Angiogenesis 1444Helmut G. Augustin






C O N T E N T S xvii

158. Tumor Blood Vessels 1457Harold F. Dvorak

159. Kaposi’s Sarcoma 1471Kimberly E. Foreman

160. Endothelial Mimicry of Placental TrophoblastCells 1479Hartmut Weiler and Rashmi Sood

161. Placental Vasculature in Health and Disease 1488S. Ananth Karumanchi and Hai-Tao Yuan

162. Endothelialization of Prosthetic Vascular Grafts 1501Thomas S. Monahan and Frank W. LoGerfo

163. The Endothelium’s Diverse Roles FollowingAcute Burn Injury 1506Rob Cartotto

164. Trauma-Hemorrhage and Its Effects on theEndothelium 1513Yukihiro Yokoyama and Irshad H. Chaudry

165. Coagulopathy of Trauma: Implications forBattlefield Hemostasis 1523Anthony E. Pusateri and John B. Holcomb

166. The Effects of Blood Transfusion on VascularEndothelium 1533Christopher G. Silliman

167. The Role of Endothelium in Erectile Functionand Dysfunction 1541Muammer Kendirci and Wayne J.G. Hellstrom

168. Avascular Necrosis: Vascular Bed/OrganStructure and Function in Health and Disease 1550Chantal Seguin

169. Molecular Control of Lymphatic SystemDevelopment 1553Darren Kafka and Young-Kwon Hong

170. High Endothelial Venules 1568Jean-Marc Gauguet, Roberto Bonasio, andUlrich H. von Andrian

171. Hierarchy of Circulating and Vessel Wall–DerivedEndothelial Progenitor Cells 1589David A. Ingram and Mervin C. Yoder

PA RT I V: D IAG N O S I S A N D T R E AT M E N T

172. Introductory Essay: Diagnosis and Treatment 1599Mansoor Husain

173. Circulating Markers of Endothelial Function 1602Andrew D. Blann, William Foster, andGregory Y.H. Lip






xviii C O N T E N T S

174. Blood Endothelial Cells 1612Robert D. Simari, Rajiv Gulati, andRobert P. Hebbel

175. Endothelial Microparticles: Biology, Function,Assay and Clinical Application 1621Yeon S. Ahn, Lawrence Horstman, Eugene Ahn,Wenche Jy, and Joaquin Jimenez

176. Molecular Magnetic Resonance Imaging 1637Susan B. Yeon, Andrea J. Wiethoff, Warren J.Manning, Elmar Spuentrup, and Rene M. Botnar

177. Real-Time Imaging of the Endothelium 1654Peter L. Gross

178. Diagnosing Endothelial Cell Dysfunction 1659Aristides Veves and Roy Freeman

179. Statins 1668James K. Liao

180. Steroid Hormones 1674James K. Liao

181. Organic Nitrates: Exogenous Nitric OxideAdministration and Its Influence on theVascular Endothelium 1682John D. Parker and Tommaso Gori

182. Therapeutic Approaches to AlteringHemodynamic Forces 1690Jose A. Adams

183. Stent- and Nonstent-Based Cell Therapy forVascular Disease 1698Michael R. Ward, Duncan J. Stewart, andMichael J.B. Kutryk

184. Building Blood Vessels 1712James B. Hoying and Stuart K. Williams

185. Gene Transfer and Expression in the VascularEndothelium 1725Michael J. Passineau and David T. Curiel

186. Drug Targeting to Endothelium 1734Vladimir R. Muzykantov

PA RT V: C HA L L E N G E S A N D O P P O RT U N I T I E S

Complexity

187. Introductory Essay: Complexity and theEndothelium 1751Ary L. Goldberger

188. Agent-Based Modeling and Applications toEndothelial Biomedicine 1754Gary An

189. Scale-Free Networks in Cell Biology 1760Eivind Almaas and Albert-Lszlo Barabsi






C O N T E N T S xix

190. Cell Fates as Attractors: Stability and Flexibilityof Cellular Phenotypes 1767Sui Huang

191. Equation-Based Models of DynamicBiological Systems 1780Gilles Clermont, Yoram Vodovotz, andJonathan Rubin

192. Vascular Control through Tensegrity-BasedIntegration of Mechanics and Chemistry 1786Donald E. Ingber

193. Simulating the Impact of Angiogenesis onMultiscale Tumor Growth Dynamics Using anAgent-Based Model 1793Chaitanya A. Athale and Thomas S. Deisboeck

Future

194. New Educational Tools for UnderstandingComplexity in Medical Science 1801Grace Huang, Michael J. Parker, and James Gordon

195. Endothelial Biomedicine: The Public HealthChallenges and Opportunities 1807George A. Mensah

196. Conclusion 1815Jane Maienshein, Manfred D. Laubichler, andWilliam C. Aird

Index 1817

Color plates appear after page 922






Editor, Associate Editors, Artistic Consultant, and Contributors

EDITOR

William C. Aird, M.D.Associate Professor of MedicineHarvard Medical SchoolChief, Division of Molecular and Vascular MedicineCenter for Vascular Biology ResearchBeth Israel Deaconess Medical CenterBoston, Massachusetts

ASSOCIATE EDITORS

Helmut G. Augustin, D.V.M., Ph.D.Department of Vascular Oncology and MetastasisGerman Cancer Research Center Heidelberg (DKFZ) and

Center for Biomedicine and Medical TechnologyMannheim (CBTM), Germany

Ary L. Goldberger, M.D.Professor of Medicine, Harvard Medical SchoolDirector, Margret and H.A. Rey Institute for Nonlinear

Dynamics in Medicine and Associate DirectorDivision of Interdisciplinary Medicine and

BiotechnologyBeth Israel Deaconess Medical CenterBoston, Massachusetts

Mansoor Husain, M.D.Director, Heart & Stroke Richard Lewar Centre of

Excellence in Cardiovascular ResearchAssociate Professor of MedicineUniversity of Toronto, TorontoOntario, Canada

Manfred D. Laubichler, Ph.D.Professor of Theoretical Biology and History of BiologyAffiliated Professor of Philosophy School of Life

Sciences and Centers for Biology and Society andSocial Dynamics and Complexity

Arizona State University TempeTempe, Arizona

Jane Maienschein, Ph.D.Regents’ Professor, President’s Professor, and Parents

Association ProfessorDirector, Center for Biology and SocietyArizona State University TempeTempe, Arizona

Jan E. Schnitzer, M.D.Scientific DirectorProfessor of Cellular & Molecular BiologyDirector of Vascular Biology & Angiogenesis

ProgramSidney Kimmel Cancer CenterSan Diego, California

Michael Simons, M.D.A.G. Huber Professor of Medicine and Pharmacology

and ToxicologyChief, Section of CardiologyDirector, Angiogenesis Research CenterDartmouth Medical School, Dartmouth Hitchcock

Medical CenterHanover, New Hampshire

ARTISTIC CONSULTANT

Steven MoskowitzAdvanced Medical GraphicsBoston, Massachusetts

CONTRIBUTORS

Md. Ruhul Abid, M.D., Ph.D.Assistant Professor of MedicineHarvard Medical SchoolDivision of Molecular and Vascular Medicine and Center

for Vascular Biology ResearchBeth Israel Deaconess Medical CenterBoston, Massachusetts

xxi






xxii E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S

Jose A. Adams, M.D.Director, Division of NeonatologyMount Sinai Medical CenterMiami Beach, Florida

Tatiana A. Afanasieva, Ph.D.Institute of PhysiologyTechnical UniversityDresden, Germany

Eugene R. Ahn, M.D.Fellow, Wallace H. Coulter LaboratoryDivision of Hematology/OncologyDepartment of MedicineUniversity of Miami School of MedicineMiami, Florida

Yeon S. Ahn, M.D.Professor of MedicineUniversity of Miami School of MedicineWallace H. Coulter LaboratoryDivision of Hematology/OncologyDepartment of MedicineMiami, Florida

William C. Aird, M.D.Associate Professor of MedicineHarvard Medical SchoolChief, Division of Molecular and Vascular MedicineCenter for Vascular Biology ResearchBeth Israel Deaconess Medical CenterBoston, Massachusetts

Eivind Almaas, Ph.D.Center for Network Research and Department

of PhysicsUniversity of Notre DameNotre Dame, Indiana

John A. Ambrose, M.D.Professor of MedicineUniversity of California at San FranciscoChief of CardiologyUniversity of California at San FranciscoFresno, California

Gary An, M.D.Assistant Professor of SurgeryDivision of Trauma/Critical CareNorthwestern University Feinberg School

of MedicineChicago, Illinois

Wadih Arap, M.D.M.D. Anderson Cancer CenterUniversity of TexasHouston, Texas

Stephen R. Archacki, M.D.Center for Cardiovascular GeneticsDepartment of Molecular CardiologyLerner Research InstituteCleveland Clinic and Cleveland State UniversityCleveland, Ohio

Chaitanya A. Athale, Ph.D.Complex Biosystems Modeling LaboratoryHarvard-MIT (HST) Athinoula A. Martinos Center for

Biomedical ImagingMassachusetts General Hospital-EastCharlestown, Massachusetts

Helmut G. Augustin, D.V.M., Ph.D.Department of Vascular Oncology and MetastasisGerman Cancer Research Center Heidelberg (DKFZ) and

Center for Biomedicine and Medical TechnologyMannheim (CBTM), Germany

Sandra Austin, Ph.D.Department of Molecular MedicineConway Institute, University College Dublin, BelfieldDublin, Ireland

Barbara J. Ballermann, M.D.Professor of MedicineCRC Chair in Endothelial Cell BiologyDirector, Division of Nephrology and ImmunologyUniversity of Alberta, EdmontonAlberta, Canada

Peter Balogh M.D., Ph.D.Department of Immunology and BiotechnologyFaculty of Medicine, University of PecsPecs, Hungary

Albert-Laszlo Barabasi, Ph.D.Emil T. Hofman Professor of PhysicsDepartment of Physics, Center for Network Research

and Department of PhysicsUniversity of Notre DameNotre Dame, Indiana

Rajat S. Barua, M.D., Ph.D.Cardiology FellowDivision of CardiologyDepartment of MedicineUniversity of California at San FranciscoFresno, California

Howard D. Beall, Ph.D.Department of Biomedical and Pharmaceutical

SciencesThe University of MontanaMissoula, Montana

Bryan Belikoff, Ph.D.New England Inflammation and Tissue

Protection InstituteNortheastern UniversityBoston, Massachusetts

Orina Belton, Ph.D.Department of Molecular Medicine,

Conway InstituteUniversity College DublinBelfield, Dublin, Ireland

Robert Benezra, Ph.D.Member, Memorial Sloan-Kettering Cancer CenterNew York, New York






E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S xxiii

Laura Benjamin, Ph.D.Associate Professor of PathologyHarvard Medical SchoolDepartment of PathologyBeth Israel Deaconess Medical CenterBoston, Massachusetts

Resham Bhattacharya, Ph.D.Department of Biochemistry and Molecular BiologyMayo Clinic College of MedicineMayo Clinic Cancer CenterRochester, Minnesota

Diane R. Bielenberg, Ph.D.Assistant Professor, Harvard Medical SchoolVascular Biology ProgramDepartment of Surgical Research, Children’s HospitalBoston, Massachusetts

Angelika Bierhaus, Ph.D.University of HeidelbergDepartment of Medicine I and Clinical ChemistryUniversity of HeidelbergHeidelberg, Germany

Kaiser M. Bijli, Ph.D.Research Associate, Division of NeonatologyDepartment of Pediatrics, School of Medicine and

DentistryUniversity of RochesterRochester, New York

David G. Binion, M.D.Associate Professor of MedicineMedical College of WisconsinDirector, IBD Center, Froedtert Memorial

Lutheran HospitalMilwaukee, Wisconsin

Miri Blank, M.D.Research Unit of Autoimmune Disease and Department

of Medicine B, Sheba Medical Center, Tel-Hashomerand the Sackler Faculty for Medicine

Tel-Aviv University, IsraelAndrew D. Blann, Ph.D.

Hemostasis Thrombosis and Vascular Biology UnitUniversity Department of Medicine, City HospitalBirmingham, United Kingdom

Natalia V. Bogatcheva, Ph.D.Vascular Biology CenterMedical College of GeorgiaAugusta, Georgia

Roberto Bonasio, Ph.D.The Immune Disease InstituteDepartment of Pathology, Harvard Medical SchoolBoston, Massachusetts

Rene M. Botnar, Ph.D.Professor of Biomedical ImagingDepartment of Nuclear MedicineTechnische Universitat MunchenMunich, Germany

Jonathan D. Brown, M.D.Cardiovascular Division, Brigham and Women’s

HospitalHarvard Medical SchoolBoston, Massachusetts

Alf O. Brubakk, M.D., Ph.D.Professor of Applied PhysiologyDepartment of Circulation and Medical ImagingNorwegian University of Science and TechnologyTrondheim, Norway

Jon A. Buras, M.D.Research Associate ProfessorNew England Inflammation and Tissue

Protection InstituteNortheastern UniversityBoston, Massachusetts

Warren W. Burggren, Ph.D.Dean, College of Arts and Sciences, Professor,

Biological SciencesUniversity of North TexasUniversity of North TexasDenton, Texas

Jane C. Burns, M.D.Professor and Chief, Division of Allergy, Immunology,

and RheumatologyDepartment of PediatricsRady Children’s Hospital San Diego and UCSD School

of MedicineLa Jolla, California

Christopher V. Carman, Ph.D.Assistant Professor of MedicineHarvard Medical SchoolDivision of Molecular and Vascular Medicine

and Center for Vascular Biology ResearchBeth Israel Deaconess Medical CenterBoston, Massachusetts

Rob Cartotto, M.D. FRCS(C)Ross Tilley Burn Centre, Sunnybrook Health

Sciences CentreDepartment of SurgeryUniversity of TorontoToronto, Ontario, Canada.

Lucy A. Carver, Ph.D.Vascular Biology & Angiogenesis ProgramSidney Kimmel Cancer CenterSan Diego, California

Anna Cattelino, Ph.D.IFOM-Fondazione Instituto FIRC di Oncologia

MolecolareMilano, Italy

Shampa Chatterjee, Ph.D.Research Assistant ProfessorPhysiologyUniversity of PennsylvaniaPhiladelphia, Pennsylvania






xxiv E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S

Irshad H. Chaudry, Ph.D.Professor of Surgery, Microbiology, Physiology &

BiophysicsVice Chairman, Department of SurgeryDirector, Center for Surgical ResearchUniversity of Alabama at BirminghamBirmingham, Alabama

Qing Chen, M.D., Ph.D.Department of ImmunologyRoswell Park Cancer InstituteBuffalo, New York

Pavan K. CheruvuMedical Student, Harvard Medical SchoolBeth Israel Deaconess Medical CenterBoston, Massachusetts

Augustine M.K. Choi, M.D.Division of PulmonaryAllergy, and Critical Care MedicineThe University of Pittsburgh School of MedicinePittsburgh, Pennsylvania

Sameer S. Chopra, Ph.D.Departments of Medicine, Pharmacology, and Cell &

Developmental BiologyVanderbilt University School of MedicineNashville, Tennessee

Aldo Ciau-Uitz, Ph.D., M.R.C.Molecular Haematology UnitThe Weatherall Institute of Molecular MedicineUniversity of Oxford, John Radcliffe Hospital,

HeadingtonOxford, United Kingdom

Kristen ClancyDepartment of ImmunologyRoswell Park Cancer InstituteBuffalo, New York

Gilles Clermont, M.D., M.Sc.Department of Critical Care MedicineUniversity of Pittsburgh Center for Inflammation and

Regenerative ModelingUniversity of PittsburghPittsburgh, Pennsylvania

J. Douglas Coffin, Ph.D.Associate Professor for Molecular GeneticsThe University of MontanaDepartment of Biomedical & Pharmaceutical SciencesMissoula, Montana

Robert Colman, M.D.Sol Sherry Professor of MedicineTemple University School of MedicinePhiladelphia, Pennsylvania

Valery Combes, Ph.D.Department of PathologyFaculty of MedicineThe University of SydneyCamperdown, Australia

Edward M. Conway, M.D., M.B.A., Ph.D.Group Leader, Professor of MedicineVIB Department of Transgene Technology and Gene

Therapy, K.U. LevenLeuven, Belgium

Judith Coppinger, Ph.D.Department of Molecular MedicineConway Institute, University College DublinDublin, Ireland

Loren Cordain, Ph.D.Department of Health and Exercise ScienceColorado State UniversityFort Collins, Colorado

Nicholas L.M. Cruden, B.Sc. (Hons), M.B., Ch.B.,M.R.C.P.

Specialist Registrar in Cardiology Universityof Edinburgh

Edinburgh, United KingdomXavier Cullere, Ph.D.

Department of PathologyCenter for Excellence in Vascular BiologyBrigham and Women’s HospitalBoston, Massachusetts

David T. Curiel, M.D., Ph.D.Division of Human Gene TherapyDepartments of Medicine, Obstetrics and

Gynecology, Pathology, Surgery, and the GeneTherapy Center

University of Alabama at BirminghamBirmingham, Alabama

Myron I. Cybulsky, M.D.Professor of Laboratory Medicine and Pathobiology,

University of TorontoSenior ScientistToronto General Research Institute,

University Health Network, TorontoOntario, Canada

Bjorn Dahlback, M.D., Ph.D.Professor of Blood Coagulation ResearchLund University Department of Laboratory MedicineClinical Chemistry, Wallenberg Laboratory, University

HospitalMalmo, Sweden

Peter F. Davies, Ph.D.Robinette Foundation Professor of Cardiovascular

Medicine, Pathology and Laboratory Medicine, andBioengineering

Director, Institute for Medicine & Engineering,University of Pennsylvania

Philadelphia, PennsylvaniaSilvia Deaglio, M.D.

Visiting Assistant ProfessorHarvard Medical SchoolBeth Israel Deaconess Medical CenterBoston, Massachusetts






E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S xxv

Thomas S. Deisboeck, M.D.Assistant Professor of RadiologyHarvard Medical SchoolDirector, Complex Biosystems Modeling LaboratoryHarvard-MIT (HST) Athinoula A. Martinos Center for

Biomedical ImagingMassachusetts General Hospital-EastCharlestown, Massachusetts

Laurie D. DeLeve, M.D., Ph.D.Professor of MedicineDivision of Gastrointestinal and Liver DiseasesUniversity of Southern California Keck School

of MedicineLos Angeles, California

H. William Detrich III, Ph.D.Professor of Biochemistry and Marine BiologyDepartment of Biology, Northeastern UniversityBoston, Massachusetts

Thomas G. Diacovo, M.D.Department of Pediatrics and PathologyColumbia University, New YorkNew York

Daniel Dumont, Ph.D.Professor, Department of Medical BiophysicsUniversity of TorontoDirector, Molecular and Cellular BiologySunnybrook Research Institute, TorontoOntario, Canada

Winston Dunn, M.D.GI Research UnitDivision of Gastroenterology and Hepatology,

Mayo ClinicRochester, Minnesota

Ann M. Dvorak, M.D.Professor of Pathology, Harvard Medical SchoolDepartment of Pathology, Beth Israel Deaconess

Medical CenterBoston, Massachusetts

Harold F. Dvorak, M.D.Professor of Pathology, Harvard Medical SchoolDepartment of Pathology, Beth Israel Deaconess


S. Boyd Eaton, M.D.Departments of Anthropology and RadiologyEmory University Atlanta, Georgia

Jay M. Edelberg, M.D., Ph.D.GlaxoSmithKline, King of Prussia, PennsylvaniaDepartment of Medicine, Weill Medical College of

Cornell University, New YorkNew York

Olav S. Eftedal, M.Sc. (Eng.), M.D., Ph.D.Department of Circulation and Medical ImagingNorwegian University of Science and TechnologyTrondheim, Norway

Arye Elfenbein, Ph.D.Angiogenesis Research CenterDartmouth Medical School, Dartmouth Hitchcock


Sharon S. Evans, Ph.D.Professor of OncologyDepartment of Immunology, Roswell Park

Cancer InstituteBuffalo, New York

Heinz Feldmann, Ph.D.Special Pathogens ProgramNational Microbiology LaboratoryPublic Health Agency of CanadaDepartment of Medical Microbiology and

Infectious DiseasesUniversity of Manitoba, WinnipegManitoba, Canada

Claire Fernandez, Ph.D.M.R.C. Molecular Haematology UnitThe Weatherall Institute of Molecular Medicine,

University of OxfordJohn Radcliffe Hospital, HeadingtonOxford, United Kingdom

Aron B. Fisher, M.D.Professor, Physiology and Medicine, Director, Institute

for Environmental MedicineUniversity of Pennsylvania Medical CenterUniversity of PennsylvaniaPhiladelphia, Pennsylvania

Danilo Fliser, M.D.Assistant Professor of MedicineDepartment of Internal MedicineDivision of NephrologyMedical School HannoverHannover, Germany

Kimberly E. Foreman, Ph.D.Associate ProfessorDepartment of PathologyBreast Cancer Research ProgramCardinal Bernardin Cancer Center, Loyola

University ChicagoMaywood, Illinois

William Foster, Ph.D.Hemostasis Thrombosis and Vascular

Biology UnitUniversity Department of MedicineCity Hospital, BirminghamUnited Kingdom

Jay W. Fox, Ph.D.Professor and Assistant Dean of Research Support,

MicrobiologyUniversity of Virginia School

of MedicineCharlottesville, Virginia






xxvi E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S

Roy Freeman, M.D.Professor of NeurologyHarvard Medical SchoolDirector, Center for Autonomic and Peripheral

Nerve DisordersBeth Israel Deaconess Medical CenterBoston, Massachusetts

Yasuhiro Funahashi, Ph.D.Department of Obstetrics and GynecologyInstitute of Cancer GeneticsColumbia University Medical Center, New YorkNew York

Daniel GaleHarvard UniversityUndergraduate Student, Beth Israel Deaconess

Medical CenterHarvard Medical SchoolBoston, Massachusetts

Joe G.N. Garcia M.D.Lowell T. Coggeshall Professor of MedicineChairman, Department of Medicine, Pritzker School

of MedicineUniversity of ChicagoChicago, Illinois

Jean-Marc Gauguet, M.D., Ph.D.The Immune Disease InstituteDepartment of PathologyHarvard Medical SchoolBoston, Massachusetts

Jean-Philippe Girard, Ph.D.Head, Laboratory of Vascular BiologyDeputy-Director, Institute of Pharmacology and

Structural Biology, CNRS UMR 5089Toulouse, France

Mark T. Gladwin, M.D.Chief, Vascular Medicine Branch, NHLBICritical Care Medicine Department, Clinical CenterNational Institutes of Health, Vascular Medicine BranchNational Heart Lung and Blood InstituteBethesda, Maryland

Ary L. Goldberger, M.D.Professor of Medicine, Harvard Medical SchoolDirector, Margret and H.A. Rey Institute for Nonlinear

Dynamics in Medicine and Associate DirectorDivision of Interdisciplinary Medicineand Biotechnology

Beth Israel Deaconess Medical CenterBoston, Massachusetts

James A. Gordon, M.D., M.P.A.Director, Gilbert Program in Medical SimulationHarvard Medical SchoolAssistant Professor of MedicineDepartment of Emergency MedicineMassachusetts General HospitalBoston, Massachusetts

Tommaso Gori, M.D., Ph.D.Department of InternalCardiovascular and Geriatric MedicineUniversity of SienaSiena, Italy

Georges E.R. Grau, M.D.Chair of Vascular ImmunologyDepartment of PathologyFaculty of MedicineThe University of SydneyCamperdown, Australia

Andreas Greinacher, M.D.Professor and Head, Department of Transfusion

MedicineInstitute of Immunology and Transfusion MedicineErnst-Moritz-Arndt-University-GreifswaldGreifswald, Germany

Marion Groger, Ph.D.Department of DermatologyDivision of General Dermatology Medical

University ViennaVienna, Austria

Peter L. Gross, M.D.St. Michael’s Hospital, University of Toronto, TorontoOntario, Canada

Rajiv Gulati M.B., Ch.B.Assistant Professor of MedicineDivision of Cardiovascular Diseases, Mayo ClinicRochester, Minnesota

Kalpna Gupta, Ph.D.Assistant ProfessorDepartment of MedicineDivision of HematologyOncology and TransplantationUniversity of Minnesota Medical SchoolMinneapolis, Minnesota

David Haig, Ph.D.Professor of BiologyDepartment of Organismic and Evolutionary

BiologyHarvard University, Cambridge, Massachusetts

Charles A. Hales, M.D.Professor of Medicine, Harvard Medical SchoolPulmonary and Critical Care Unit, Department

of MedicineMassachusetts General HospitalBoston, Massachusetts

Mitchell L. Halperin, M.D.Emeritus Professor of MedicineUniversity of TorontoDivision of Nephrology, St. Michael’s Hospital, TorontoOntario, Canada

Hans-Peter Hammes, M.D., Ph.D.Department of Medicine V, University of MannheimGermany






E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S xxvii

Shivalika Handa, Ph.D.Candidate, Department of Laboratory Medicine &

PathobiologyUniversity of Toronto, TorontoOntario, Canada.

Per M. Haram, M.D., Ph.D.Department of Circulation and Medical ImagingNorwegian University of Science and TechnologyTrondheim, Norway

Alan R. Hargens, Ph.D.Professor of Orthopaedic SurgeryUniversity of California, San DiegoUCSD Medical CenterSan Diego, California

Elizabeth O. Harrington, Ph.D.Pulmonary Vascular Research Laboratory, Providence VA

Medical CenterAssociate Professor of MedicineThe Warren Alpert Medical School of

Brown UniversityProvidence, Rhode Island

Ossama A. Hatoum, M.D.Froedtert Memorial Lutheran HospitalMedical College of WisconsinMilwaukee, Wisconsin

Gary J. HausmanResearch Physiologist, USDA – ARS and University

of GeorgiaAthens, Georgia

Robert P. Hebbel, M.D.Regents Professor, George Clark ProfessorVice-Chairman for ResearchDepartment of MedicineDirector, Vascular Biology Center, University of

MinnesotaMinneapolis, Minnesota

Wayne J.G. Hellstrom, M.D.Professor of UrologyChief, Section of Andrology Tulane University Health

Sciences CenterDepartment of UrologyNew Orleans, Louisiana

Erik Henke, Ph.D.Memorial Sloan-Kettering Cancer Center,

New YorkNew York

Timothy Hla, Ph.D.Professor of Cell BiologyDirector, Center for Vascular Biology, University of

Connecticut Health CenterFarmington, Connecticut

Laszlo M. Hoesel, M.D.University of Michigan Health SystemsDepartment of PathologyAnn Arbor, Michigan

John B. Holcomb, M.D., F.A.C.S., C.O.L., M.C.U.S. Army, Clinical Professor of Surgery, University of

Texas Health Science Center, San AntonioTexas Trauma Consultant for The Surgeon General,

CommanderCommander, U.S. Army Institute of Surgical ResearchFort Sam Houston, Texas

Anthony Hollenberg, M.D.Associate Professor of MedicineHarvard Medical SchoolChief, Thyroid Unit, Beth Israel Deaconess


Young-Kwon Hong, Ph.D.Assistant Professor, Department of Surgery and

Biochemistry & Molecular BiologyNorris Comprehensive Cancer CenterUniversity of Southern CaliforniaLos Angeles, California

Lawrence Horstman, BSResearch Associate, Wallace H. Coulter LaboratoryDivision of Hematology/OncologyDepartment of MedicineUniversity of Miami School of MedicineMiami, Florida

James B. Hoying, Ph.D.Associate Professor, Department of SurgeryUniversity of LouisvilleChief, Division of Cardiovascular TherapeuticsCardiovascular Innovation InstituteLouisville, Kentucky

Grace Huang, M.D.Instructor in Medicine, Harvard Medical SchoolDirector, Office of Educational Technology, Shapiro

Institute for Education and ResearchBeth Israel Deaconess Medical CenterBoston, Massachusetts

Sui Huang, M.D., Ph.D.Assistant Professor of Surgery, Vascular Biology

ProgramDepartment of SurgeryChildren’s Hospital, Harvard Medical School, Boston and

Harvard Stem Cell InstituteCambridge, Massachusetts

Deborah A. Hughes, Ph.D.Department of Biochemistry and Molecular BiologyMayo Clinic College of MedicineMayo Clinic Cancer CenterRochester, Minnesota

Mansoor Husain, M.D.Director, Heart & Stroke Richard Lewar Centre of

Excellence in Cardiovascular ResearchAssociate Professor of MedicineUniversity of Toronto, TorontoOntario, Canada






xxviii E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S

Richard O. Hynes, Ph.D.Center for Cancer Research and Howard Hughes

Medical InstituteMassachusetts Institute of TechnologyCambridge, Massachusetts

Jose M. IcardoDepartment of Anatomy and Cell BiologyUniversity of CantabriaSantander, Spain

Donald E. Ingber, M.D., Ph.D.Judah Folkman Professor of Vascular BiologyDepartment of Pathology, Harvard Medical SchoolVascular Biology Program, Departments of Surgery

and PathologyChildren’s Hospital, Boston, Massachusetts

David A. Ingram, M.D.Department of Pediatrics, Herman B. Wells Center for

Pediatric ResearchIndiana University School of MedicineIndianapolis, Indiana

Kaikobad Irani, M.D.Associate Professor of Medicine, Cardiovascular Institute

University of Pittsburgh Medical CenterPittsburgh, Pennsylvania

Mukesh K. Jain, M.D.Case Western Reserve UniversityCleveland, Ohio

Joaquin J. Jimenez, M.D.Assistant Professor of Medicine, Wallace H. Coulter

Laboratory Division of Hematology/OncologyDepartment of MedicineUniversity of Miami School of MedicineMiami, Florida

Peter Lloyd Jones, Ph.D.Associate Professor of Pathology & Laboratory MedicineDirector, Penn-CMREF Center for Pulmonary

Hypertension ResearchInstitute for Medicine & EngineeringUniversity of Pennsylvania, Philadelphia

Klaus D. Jurgens, Ph.D.Professor of Physiology, Zentrum Physiologie,

Medizinische HochschuleHannover, Germany

Wenche Jy, Ph.D.Assistant Professor of MedicineWallace H. Coulter Laboratory Division of

Hematology/OncologyDepartment of Medicine, University of Miami School

of MedicineMiami, Florida

Darren Kafka, Ph.D.Department of Surgery and Norris Comprehensive

Cancer CenterKeck School of Medicine, University of Southern

CaliforniaLos Angeles, California

Kamel S. Kamel, M.D.Professor of Medicine, University of Toronto,

St. Michael’s HospitalToronto, Ontario, Canada

Kenneth L. KaplanAssociate Director, Collaborative Initiatives at MITAssociate Director, Urban Design Lab,

Earth InstituteColumbia University

Kai Kappert, M.D.Cancer Centrum KarolinskaDepartment of Oncology-Pathology,

Karolinska InstitutetStockholm, Sweden

S. Ananth Karumanchi, M.D.Associate Professor of MedicineHarvard Medical School, Beth Israel Deaconess


Jaswinder Kaur, Ph.D.Candidate, Department of Physiology and

BiophysicsUniversity of Calgary, CalgaryAlberta, Canada

Muammer Kendirci, M.D.Department of Urology, Sisli Etfal Training and

Research HospitalIstanbul, Turkey

Levon M. Khachigian, Ph.D., D.Sc.Professor and Head Transcription and Gene Targeting

Laboratory Centre for Vascular ResearchPrince of Wales HospitalUniversity of New South WalesSydney, Australia

Jan T. KielsteinAssistant Professor of MedicineStanford University Medical SchoolFalk Cardiovascular Research Center, Stanford,

California; and Department of Internal Medicine,Division of Nephrology

Medical School Hannover, GermanyHong Pyo Kim, Ph.D.

Division of Pulmonary, Allergy, and CriticalCare Medicine

The University of Pittsburgh Schoolof Medicine

Pittsburgh, PennsylvaniaRolf Kinne, M.D., Ph.D.

Max Planck Institut fur Molekulare PhysiologieDortmund, Germany

Jan Kitajewski, Ph.D.Departments of Pathology and Obstetrics and

GynecologyInstitute of Cancer Genetics, Columbia University

Medical Center, New YorkNew York






E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S xxix

Michael Klagsbrun, Ph.D.Patricia K. Donahoe Professor of SurgeryDepartment of Surgery, Harvard Medical SchoolVascular Biology Program, Children’s HospitalBoston, Massachusetts

Karolina Kolodziejska, Ph.D.Candidate, Department of Laboratory Medicine &

PathobiologyUniversity of Toronto, TorontoOntario, Canada

Peter Koopman, Ph.D.Institute for Molecular BioscienceThe University of QueenslandBrisbane, Australia

Paul Kubes, Ph.D.Director, Institute of Infection, Immunity and

InflammationDepartment of Physiology and BiophysicsUniversity of Calgary, CalgaryAlberta, Canada

Frank Kuhnert, Ph.D.Postdoctoral Fellow, Department

of MedicineDivision of HematologyStanford University School of MedicineStanford, California

Rainer Kunstfeld, M.D.Department of DermatologyDivision of General Dermatology, Medical

University ViennaVienna, Austria

Peter Kurschat, Ph.D.Harvard Medical SchoolVascular Biology Program, Department of Surgical

Research, Children’s HospitalBoston, Massachusetts

Michael J.B. Kutryk, M.D., Ph.D.The Terrence Donnelly Vascular Biology

LaboratoriesSt. Michael’s Hospital, and The McLaughlin Centre for

Molecular Medicine and the Departmentof Medicine

University of Toronto, TorontoOntario, Canada

Eckhard Lammert, Ph.D.Max Planck Institute of Molecular Cell Biology and

GeneticsDresden, Germany

Manfred D. Laubichler, Ph.D.Professor of Theoretical Biology and History

of BiologyAffiliated Professor of Philosophy School of Life Sciences

and Centers for Biology and Society and SocialDynamics and Complexity Arizona State UniversityTempe

Tempe, Arizona

Jeffrey Laurence, M.D.Professor of Medicine, Weill Medical College of Cornell

UniversityAttending Physician, New York Presbyterian

HospitalNew York, New York

Jack Lawler, Ph.D.Professor of Pathology, Harvard Medical SchoolDepartment of Pathology, Beth Israel Deaconess


Michelle Letarte, Ph.D.Molecular Structure and Function, Hospital for Sick

Children, University of Toronto, TorontoOntario, Canada

Marcel Levi, M.D., Ph.D.Professor of Medicine, University of AmsterdamChairman, Department of MedicineAcademic Medical Center, AmsterdamThe Netherlands

Dean Y. Li, M.D.Department of Oncological SciencesProgram in Human Molecular Biology and GeneticsDivision of Cardiology, School of Medicine, University

of UtahSalt Lake City, Utah

Jian Li, M.D., Ph.D.Assistant Professor of MedicineHarvard Medical SchoolDivision of Cardiology, Beth Israel Deaconess


James K. Liao M.D.Associate Professor of MedicineHarvard Medical SchoolDirector, Vascular Medicine Research, Brigham and

Women’s HospitalBoston, Massachusetts

Andrew H. Lichtman, M.D., Ph.D.Associate Professor of Pathology, Harvard Medical

SchoolDepartment of Pathology, Brigham and Women’s

HospitalBoston, Massachusetts

Stefan Liebner, Ph.D.Institute of Neurology, University FrankfurtFrankfurt, Germany

Zhiyong Lin, Ph.D.Case Western Reserve UniversityCleveland, Ohio

Gregory Y.H. Lip, M.D.Consultant Cardiologist and Professor of Cardiovascular

MedicineDirector – Haemostasis Thrombosis & Vascular Biology

Unit, University Department of MedicineCity Hospital, Birmingham, United Kingdom






xxx E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S

Robert Loewe, M.D.Department of DermatologyDivision of General Dermatology Medical University

ViennaVienna, Austria

Frank W. LoGerfo, M.D.William V. McDermott Professor of SurgeryHarvard Medical SchoolChief, Division of Vascular SurgeryBeth Israel Deaconess Medical CenterBoston, Massachusetts

Jin Ning Lou, Ph.D.Institute of Clinical Medical SciencesChina-Japan Friendship HospitalBeijing, China

Charles J. Lowenstein, M.D.Professor, Departments of Medicine

and PathologyThe Johns Hopkins University School

of MedicineBaltimore, Maryland

Qing Lu, Ph.D.Pulmonary Vascular Research LaboratoryProvidence VA Medical CenterAssistant Professor of MedicineThe Warren Alpert Medical School of

Brown UniversityProvidence, Rhode Island

F. William Luscinskas, Ph.D.Associate Professor of MedicineHarvard Medical SchoolBrigham and Women’s HospitalBoston, Massachusetts

Nigel Mackman, Ph.D.John Parker Professor of MedicineUniversity of North Carolina at

Chapel HillChapel Hill, North Carolina.

Patricia B. Maguire, Ph.D.Molecular Medicine Group, Conway InstituteSchool of Medicine and Medical ScienceUniversity College DublinDublin, Ireland

Jane Maienschein, Ph.D.Regents’ Professor, President’s Professor, and Parents

Association ProfessorDirector, Center for Biology and Society, Arizona State

University TempeTempe, Arizona

Mark W. Majesky, Ph.D.Professor, Departments of Medicine & Genetics,

Associate DirectorCarolina Cardiovascular Biology CenterUniversity of North Carolina at

Chapel HillChapel Hill, North Carolina

Warren J. Manning, M.D.Professor of Medicine and RadiologyHarvard Medical SchoolSection Chief, Non-invasive Cardiac Imaging, Beth Israel

Deaconess Medical CenterBoston, Massachusetts

Mark Martinez, M.D.Instructor in Medicine, University of Utah School

of MedicineSalt Lake City, Utah

Alan E. Mast M.D., Ph.D.Investigator, Blood Research InstituteThe Blood Center of WisconsinMilwaukee, Wisconsin

Tanya Mayadas, Ph.D.Associate Professor of Pathology, Harvard Medical SchoolDepartment of PathologyCenter for Excellence in Vascular Biology, Brigham and

Women’s HospitalBoston, Massachusetts

Joseph H. McCarty, Ph.D.Department of Cancer Biology, Unit 173,University of Texas – M. D. Anderson Cancer Center,

1515 Holcombe Boulevard,Houston, Texas

Rodger P. McEver, M.D.Eli Lilly Distinguished Chair in Biomedical Research,

Member and HeadCardiovascular Biology Research ProgramOklahoma Medical Research FoundationOklahoma City, Oklahoma

John H. McVey, Ph.D.Group Leader Haemostasis and Thrombosis, Reader in

Haemostasis and ThrombosisMRC Clinical Sciences Centre, Imperial College London,

Hammersmith Hospital CampusLondon, United Kingdom

Janice V. Meck, Ph.D.NASA/Johnson Space CenterHouston, Texas

George A. Mensah, M.D., F.A.C.P., F.A.C.C., F.C.P. (SA) HonDistinguished Scientist, Heart Disease and Stroke

Prevention, National Center for Chronic DiseasePrevention and Health Promotion, Centers forDisease Control and Prevention

Atlanta, GeorgiaChristine N. Metz, Ph.D.

Associate Investigator, Director, Laboratory of MedicinalBiochemistry

The Feinstein Institute for Medical Research, NorthShore-LIJ Health System

Manhasset, New YorkValerie C. Midgley, Ph.D.

Center for Vascular Research, Prince of Wales HospitalUniversity of New South WalesSydney, Australia






E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S xxxi

Takashi Mikawa, Ph.D.Department of Cell and Developmental

BiologyCornell University Medical CollegeNew York, New York

Ronald W. Millard, Ph.D.Professor of Pharmacology & Cell BiophysicsUniversity of Cincinnati College of MedicineCincinnati, Ohio

David Milstone, Ph.D.Department of Pathology, Brigham and Women’s

Hospital, Harvard Medical SchoolBoston, Massachusetts

Takashi Minami, Ph.D.Associate Professor, University of TokyoTokyo, Japan

Jamie Mitchell, M.D.Beth Israel Deaconess Medical CenterHarvard Medical SchoolBoston, Massachusetts

Aigul Moldobaeva, Ph.D.Research Associate, Division of Pulmonary and Critical

Care MedicineJohns Hopkins Asthma and Allergy CenterJohns Hopkins UniversityBaltimore, Maryland

Bruce Molitoris, M.D.Division of NephrologyIndiana Center for Biological MicroscopyIndiana University School of MedicineIndianapolis, Indiana

Thomas S. Monahan, M.D.Division of Vascular SurgeryBeth Israel Deaconess Medical CenterBoston, Massachusetts

Craig N. Morrell, Ph.D.Departments of Pathology and Comparative

MedicineThe Johns Hopkins University School

of MedicineBaltimore, Maryland

Steven MoskowitzAdvanced Medical GraphicsBoston, Massachusetts

Debabrata Mukhopadhyay, Ph.D.Professor, Department of Biochemistry and Molecular

BiologyMayo Clinic College of MedicineMayo Clinic Cancer CenterRochester, Minnesota

Masahiro Murakami, M.D., Ph.D.Angiogenesis Research Center & Section

of CardiologyDartmouth Medical SchoolDartmouth Hitchcock Medical CenterHanover, New Hampshire

Silvia Muro, Ph.D.Research Assistant Professor of PharmacologyInstitute for Translational Medicine and TherapeuticsInstitute for Environmental MedicineUniversity of Pennsylvania Medical SchoolPhiladelphia, Pennsylvania

Allan G. Murray, M.D.Associate Professor of MedicineUniversity of Alberta, EdmontonAlberta, Canada

Vladimir R. Muzykantov M.D., Ph.D.Associate Professor of Pharmacology and MedicineDirector, Targeted Therapeutics Program, Institute of

Translational Medicine and Therapeutics (ITMAT)Sr. Investigator, Institute for Environmental Medicine

(IFEM)University of Pennsylvania School of MedicinePhiladelphia, Pennsylvania

Peter P. Nawroth, M.D.University of HeidelbergDepartment of Medicine I and Clinical ChemistryUniversity of HeidelbergHeidelberg, Germany

Randolph M. Nesse, M.D.Professor of PsychiatryUniversity of MichiganAnn Arbor, Michigan

Debra K. Newman, Ph.D.Associate Investigator, Blood Research InstituteThe Blood Center of WisconsinMilwaukee, Wisconsin

Peter J. Newman, Ph.D.Vice President for ResearchWalter A. Schroeder Associate Director, Blood Research

InstituteThe Blood Center of WisconsinMilwaukee, Wisconsin

Mark R. Nicolls, M.D.Associate Professor of MedicinePulmonary and Critical Care Medicine DivisionUniversity of Colorado at Denver and Health Sciences

CenterDenver, Colorado

Anne Nicholson-Weller, M.D.Professor of MedicineHarvard Medical SchoolDivisions of Allergy/Inflammation and Infectious

DiseasesBeth Israel Deaconess Medical CenterBoston, Massachusetts

Max Nieuwdorp, Ph.D.Department of Vascular MedicineCardiovascular Research Institute AmsterdamAcademic Medical Center and University

of AmsterdamAmsterdam, The Netherlands






xxxii E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S

Niaobh O’Donoghue, Ph.D.Department of Molecular MedicineConway Institute, University College DublinDublin, Ireland

Dessy Nikova, Ph.D.Institute of PhysiologyWestfalia Wilhelms UniversityMuenster, Germany

Peter Oettgen, M.D.Associate Professor of MedicineHarvard Medical SchoolDivision of CardiologyDivision of Molecular and Vascular Medicine, and

Center for Vascular Biology ResearchBeth Israel Deaconess Medical Center, Boston

Kenneth R. Olson, Ph.D.Professor of Physiology, Indiana University School of

Medicine – South Bend, South Bend, IndianaArne Ostman, Ph.D.

Professor of Molecular Oncology, Cancer CentrumKarolinska

Department of Oncology-Pathology, KarolinskaInstitutet

Stockholm, SwedenSareh Parangi, M.D.

Assistant Professor of SurgeryHarvard Medical SchoolDepartment of Surgery, Beth Israel Deaconess Medical

CenterBoston, Massachusetts

Kye Won Park, Ph.D.Department of Oncological SciencesProgram in Human Molecular Biology and GeneticsUniversity of UtahSalt Lake City, Utah

John D. Parker, M.D., F.R.C.P.(C)Professor of Medicine and Pharmacology, University of

TorontoHead, Division of Cardiology, Department

of MedicineUniversity Health Network and Mount Sinai HospitalToronto, Ontario, Canada

Michael J. Parker, M.D.Assistant Professor of Medicine, Harvard Medical SchoolDivision of Pulmonary and Critical Care MedicineBeth Israel Deaconess Medical CenterBoston, Massachusetts

Renata Pasqualini, Ph.D., M.D.Anderson Cancer Center, University of TexasHouston, Texas

Michael J. Passineau, Ph.D.Division of Human Gene TherapyDepartments of Medicine, Obstetrics and Gynecology,

Pathology, Surgery, and the Gene Therapy CenterUniversity of Alabama at BirminghamBirmingham, Alabama

Roger Patient, Ph.D.M.R.C. Molecular Haematology UnitThe Weatherall Institute of Molecular MedicineUniversity of OxfordJohn Radcliffe HospitalHeadington, United Kingdom

Cam Patterson, M.D., F.A.C.C.Professor of Medicine (Cardiology), Pharmacology, and

Cell and Developmental BiologyThe University of North Carolina at Chapel HillChief, Division of CardiologyDirector, Carolina Cardiovascular Biology CenterNorth Carolina

Knut Pettersson, Ph.D.Athera Biotechnologies, Fogdevreten 2b, SE-171 77

StockholmSweden

Peter Petzelbauer, M.D.Department of DermatologyDivision of General Dermatology Medical University

ViennaVienna, Austria

Jorge Plutzky, M.D.Cardiovascular DivisionAssociate Professor of MedicineHarvard Medical SchoolBrigham and Women’s HospitalBoston, Massachusetts

Jordan S. Pober, M.D., Ph.D.Professor of Immunobiology, Pathology and

DermatologyVice-Chair of Immunobiology for Human and

Translational ImmunologyYale University School of MedicineNew Haven, Connecticut

Thomas J. Poole, Ph.D.Department of Cell and Developmental BiologySUNY Upstate Medical UniversitySyracuse, New York

Sonja Praprotnik, Ph.D.University Clinical CenterLjubljana, Slovenia

Dexter PrattVP Knowledge Modeling, Genstruct Inc.Cambridge, Massachusetts

Ralph E. Purdy, Ph.D.Department of Pharmacology University of California,

IrvineIrvine, California

Anthony E. Pusateri, Ph.D.Associate Director, Novo Nordisk Research U.S.North Brunswick, New Jersey

Susan E. Quaggin, M.D.Associate Professor of Medicine, University of TorontoMt. Sinai Hospital, University of Toronto, TorontoOntario, Canada






E D I T O R , A S S O C I A T E E D I T O R S , A R T I S T I C C O N S U L T A N T , A N D C O N T R I B U T O R S xxxiii

Deborah A. Quinn, M.D.Assistant Professor of MedicineHarvard Medical SchoolPulmonary and Critical Care UnitDepartment of Medicine, Massachusetts General

HospitalBoston, Massachusetts

Jacob H. Rand, M.D.Hematology Laboratory, Montefiore Medical CenterBronx, New York

Arshad Rahman, Ph.D.Associate Professor of Pediatrics, Division of

NeonatologyDepartment of Pediatrics, School of Medicine and

DentistryUniversity of RochesterRochester, New York

May J. Reed, M.D.Associate Professor, Department of MedicineDivision of Gerontology and Geriatric MedicineUniversity of WashingtonSeattle, Washington

Wende R. Reenstra, M.D.Research Associate Professor, New England

Inflammation and Tissue Protection InstituteNortheastern UniversityBoston, Massachusetts

Carl L. Reiber, Ph.D.Associate Dean, College of SciencesProfessor, School of Life SciencesUniversity of NevadaLas Vegas, Nevada

John M. Rhodes, Ph.D.Angiogenesis Research Center & Section of CardiologyDartmouth Medical School, Dartmouth Hitchcock


Simon C. Robson, M.D.Professor of MedicineHarvard Medical SchoolBeth Israel Deaconess Medical CenterBoston, Massachusetts

Sharon Rounds, M.D.Pulmonary Vascular Research Laboratory, Providence VA

Medical CenterProfessor of Medicine and of Pathology and Laboratory

MedicineThe Warren Alpert Medical School of Brown UniversityProvidence, Rhode Island

Jonathan Rubin, Ph.D.Department of Mathematics, University of Pittsburgh,

PittsburghPennsylvania Center for Inflammation and Regenerative

ModelingUniversity of PittsburghPittsburgh, Pennsylvania

John E. Rush, D.V.M., M.S.Department of Clinical Sciences, Cummings School of

Veterinary Medicine at Tufts UniversityNorth Grafton, Massachusetts

Stefan W. Ryter, Ph.D.Division of Pulmonary, Allergy, and Critical Care

MedicineThe University of Pittsburgh School

of MedicinePittsburgh, Pennsylvania

Paul W. Sanders, M.D.Nephrology Research and Training Center,

Comprehensive Cancer Center, and Cell Adhesionand Matrix Research Center

Division of Nephrology, Professor of Medicine andPhysiology & Biophysics and AM Chief

VA Renal Section, Department of Medicine, andDepartment of Physiology & Biophysics

University of Alabama at BirminghamBirmingham, and Department of Veterans Affairs

Medical CenterBirmingham, Alabama

Gernot Schabbauer, Ph.D.Departments of Immunology and Cell BiologyThe Scripps Research InstituteLa Jolla, California

Herrmann Schillers, Ph.D.Institute of Physiology, Westfalia Wilhelms UniversityMuenster, Germany

Ann Marie Schmidt, M.D.College of Physicians and Surgeons, Columbia

University, New YorkNew York

Hans-Joachim Schnittler, M.D.Institut fur PhysiologieTechnische Universitat, Medizinische; Fakultat;

Fetcherstraβe 74Dresden, Germany

Jan E. Schnitzer, M.D.Scientific Director, Professor of Cellular & Molecular

Biology Director of Vascular Biology & AngiogenesisProgram

Sidney Kimmel Cancer CenterSan Diego, California

Daniel L. Schodek, Ph.D.Professor of Architectural TechnologyDepartment of Architecture, Harvard Design SchoolCambridge, Massachusetts

Anthony Sebastian, M.D.Department of Medicine, Division of NephrologyClinical and Translational Science InstituteUniversity of California – San FranciscoSan Francisco, California

Jochen Seebach, Ph.D.Institute of Physiology, Technical UniversityDresden, Germany






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