prelims (vol. 1) - elsevier.com
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VOLUME 1
Foreword I by Shu Chien vForeword II by Bruce Zetter viiIntroduction ixEditorial Board Members xiiiContributors xv
PART IBASIC SCIENCE
Section A: Cell Biology
CHAPTER 1Endothelin in the Microvasculature 5Matthias Barton
IntroductionEndothelins: Vasoactive PeptidesRegulatory Role of Endothelin for Microvascular FunctionEndothelin and the Microvasculature in Disease
CHAPTER 2Control of Cell Motility by the Cytoskeleton and Extracellular Matrix 13Amy Brock and Donald E. Ingber
IntroductionDirectional MotilityThe Migratory ProcessControl of Motility by ECMBiochemical Signaling MechanismsMechanical Signaling MechanismsFuture Directions
CHAPTER 3Ultrastructural Morphometry of Capillary Basement Membrane Thickness 19Edward C. Carlson
IntroductionUltrastructural DefinitionsCapillary Basement Membrane Thickness in Health and
DiseaseCapillary Basement Membrane Morphometric MethodsConclusions
CHAPTER 4IL-7 Receptor and MicrovascularEndothelial Cells 25Danuta Dus, Agnieszka Krawczenko, and Claudine Kieda
Receptor for IL-7
CHAPTER 5Matrix Metalloproteinases, Tissue Inhibitors of Metalloproteinases, and the Microvasculature 29Cecilia A. Fernández and Marsha A. Moses
Matrix MetalloproteinasesTissue Inhibitors of Metalloproteinases
CHAPTER 6Matrix Metalloproteinases and Their Inhibitors 33Iwona Fijalkowska and Rubin M. Tuder
IntroductionMolecular StructureActivation of MetalloproteinasesSpecific Inhibitors of Metalloproteinases: TIMPsMMP Genes and Regulation of ExpressionAngiogenesisMMPs and Pulmonary Vascular DiseasesConclusion
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CHAPTER 7VEGF-A and its Isoforms 41Eric B. Finkelstein and Patricia A. D’Amore
VEGF Isoform StructureVEGF and the ECMVEGF–Receptor InteractionsIsoform ExpressionIsoform FunctionConclusion
CHAPTER 8Ephrins and the Unveiling of Distinct Arterial and Venous Microcirculations 47Jeffrey M. Gelfand and Guillermo García-Cardeña
IntroductionCell Signaling Via Ephrins and Eph ReceptorsAngiogenesis Requires Ephrin SignalingEphrins Reveal Distinct Arterial and Venous Microvascular
IdentitiesThe Implications of a New Microvascular Paradigm
CHAPTER 9Endothelial Heterogeneity 51Mary E. Gerritsen
IntroductionEndothelial Architecture
CHAPTER 10Portholes on a Vessel: Endothelial Fenestrae 57Sofia Ioannidou, Steven J. Samuelsson, and David T. Shima
Fenestrae StructureFenestrae BiogenesisFenestrae FunctionChallenges for the Future
CHAPTER 11Neuropilins and the Vasculature 63Roni Mamluk and Michael Klagsbrun
IntroductionNeuropilin StructureEndothelial Cell NeuropilinNeuropilin Function in Developmental AngiogenesisNeuropilin in Pathological AngiogenesisSummary
CHAPTER 12Receptor Tyrosine Kinase Signal Transduction in the Microvasculature 69Marie B. Marron and Nicholas P. J. Brindle
IntroductionSignaling by VEGF ReceptorsSignaling by FGF ReceptorsThe Ephs and EphrinsSignaling by the Tie Receptor Tyrosine KinasesConclusion
CHAPTER 13Eicosanoids and the Pulmonary Microvasculature 77Ivan M. Robbins and Brian W. Christman
IntroductionPulmonary Arterial HypertensionClinical Modulation of Eicosanoids in Pulmonary Vascular
Disease
Section B: Vascular Development: Vasculogenesis and Angiogenesis
CHAPTER 14Role of Platelet-Derived Growth Factors in the Microvasculature 85Christer Betsholtz and Holger Gerhardt
SummaryIntroductionRoles of PDGFs in the Microvasculature Revealed by
Genetic StudiesPericyte Density and Its Relationship to Organ Pathology
CHAPTER 15Basic Concepts of Intussusceptive Angiogenesis 91Valentin Djonov and Peter H. Burri
Sprouting and Intussusceptive AngiogenesisThe Basic Concept of IntussusceptionHallmarks of IntussusceptionThree Facets of Intussusceptive AngiogenesisSprouting and Intussusception: Two Complementary
Angiogenic MechanismsSummary
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CHAPTER 16Vascular Permeability Factor/Vascular Endothelial Growth Factor(VPF/VEGF, VEGF-A) 97Harold F. Dvorak
VEGF-A StructureVEGF-A Receptors and Signaling PathwaysBiological ActivitiesExpression of VEGF-A in Normal Physiology and
in PathologyRegulation of VEGF-A ExpressionThe New Blood Vessels Induced by VEGF-AClinical significance of VEGF-A
CHAPTER 17Endothelial Progenitor Cells, Vasculogenesis, and Their Contribution to New Blood Vessel Formation in the Adult 105John Glod and Howard A. Fine
IntroductionMature Endothelial Cells in the CirculationEndothelial Progenitor Cells from the Bone MarrowIsolation and Characterization of Circulating Endothelial
Progenitors from Adult Peripheral BloodContribution of Circulating Cells to NeovasculatureFactors That Influence the Numbers of Circulating
Endothelial ProgenitorsAre Circulating Cells Critical to the Formation of
New Vasculature?Clinical Studies Using Bone Marrow–Derived Cells to
Augment NeovascularizationUsing Bone Marrow–Derived Cells in Antiangiogenic
StrategiesConclusion
CHAPTER 18Pericytes and MicrovascularMorphogenesis 111Ira M. Herman
OverviewMicrovascular MorphogenesisReceptor Kinases Regulate Microvascular Growth and
DifferentiationPathologic Angiogenesis: Recapitulation of Microvascular
DevelopmentThe Isoactin Network Drives Retinal Microvascular
MorphogenesisRho GTPases Signal Isoactin-Dependent Cytoskeletal
Remodeling
CHAPTER 19PDGF-B and Pericyte Recruitment 117Michael J. Jarzynka and Shi-Yuan Cheng
Vasculogenesis and AngiogenesisPlatelet-Derived Growth FactorPDGF-B, Pericyte Recruitment, and Vessel MaturationThe Role of PDGF-B in Tumor Angiogenesis and
Progression
CHAPTER 20VEGF Regulation of Morphogenesis 121Thomas J. Poole and Eric B. Finkelstein
Origins of the Embryonic Vascular PatternAngioblast InductionVasculogenesisEmbryonic AngiogenesisOther Functions of VEGF in MorphogenesisSummary
CHAPTER 21The Two-Phase Model for Angiogenesis Regulation by the Extracellular Matrix 127James D. San Antonio and Renato V. Iozzo
IntroductionPhase I: Maintenance of Quiescence by the Basement
MembraneThe Transition Between the Matrix Phases: Growth Factors
and MMPs Provide the One-Two PunchPhase II: Induction of Capillary Morphogenesis by the
Interstitial Matrices, Fibrillar Collagens or FibrinTissue Engineering of the Microvasculature: The ECM
Holds the KeyECM Templates for Microvascular EngineeringRational Engineering and Use of Angiogenic Polymers
CHAPTER 22Pericytes and Glial Cells and Vascular Development 137Stanley A. Vinores and John D. Ash
IntroductionPericytesAstrocytes
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Section C: In Vivo Models
CHAPTER 23Hemangioma: A Model System to Study Growth and Regression of Blood Vessels 145Joyce Bischoff
Clinical Features of HemangiomaLife Cycle of HemangiomaSummary
CHAPTER 24Window Models 151Dai Fukumura
SummaryIntroductionChronic Window PreparationsUtilization of Window ModelsFuture Perspectives
CHAPTER 25The Cremaster Muscle forMicrocirculatory Studies 159Robert Hester
Animal ModelsCardiovascular ParametersModels of HypertensionConclusion
CHAPTER 26Zebrafish: A Model for Studying Microvascular Development and Function 165Kameha Kidd and Brant Weinstein
Emergence of the Zebrafish as a Vertebrate Genetic ModelFrom Phage to FishThe Zebrafish as a Model Organism for Studying Vessel
FormationConclusions
CHAPTER 27The Significance of the Nail Fold in Clinical and Experimental Studies 173Hildegard Rand Maricq
Definition and Description of the Nail FoldPlace of the Nail Fold in Human Microvascular StudiesMethodsData ObtainedExperimental StudiesClinical StudiesConclusions
CHAPTER 28Capillaries in the Chicken Chorioallantoic Membrane 181Domenico Ribatti and Marco Presta
Developmental Anatomy of the Blood Vessels of the CAMStructure of the Blood Vessels of the CAMEndogenous CAM modulators of Blood Vessel FormationCAM as a model to Study the Modulation of AngiogenesisConcluding Remarks
CHAPTER 29The Cremaster Muscle as a Microvascular Research Model 187Maria Siemionow and Andrea Moreia-Gonzalez
BackgroundApplication of the Cremaster Muscle Island Flap for
Ischemia-Reperfusion and Related StudiesApplication of the Cremaster Muscle for Chronic
Observation of the MicrocirculationMicrocirculatory Responses to Cremaster Muscle
DenervationA Model of Cremaster Muscle Isograft and Allograft
TransplantCremaster Muscle Model for Tumor Implantation
CHAPTER 30The Hamster Cheek Pouch as a Research Model of Inflammation 195Erik Svensjö
MorphologyCheek Pouch PreparationChanges in Vascular PermeabilityInhibition of Mediator-Induced Macromolecular LeakageConclusions
Section D: Permeability, Tone andHemodynamics
CHAPTER 31Regulation of MicrovascularPermeability 203D. O. Bates
IntroductionMicrovascular Permeability to Water: Hydraulic
Conductivity (Lp).Microvascular Permeability to SolutesNormal—or Baseline—Vascular PermeabilityAgonist-Mediated Increased Vascular Permeability
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CHAPTER 32Regulation of Vascular Endothelial Cell Signal Transduction and Phenotype by Mechanical Factors 209Konstantin G. Birukov
Mechanical Forces Acting on Vascular EndotheliumMechanosensors and Signal Transduction PathwaysEffect of Mechanical Stimulation on Endothelial
Phenotype and Gene Expression ProfileConcluding Remarks
CHAPTER 33Autacoid Production by Hemodynamic Forces 215Ingrid Fleming
Autacoid Production by Hemodynamic ForcesEndothelium-Derived AutacoidsHemodynamic Forces and the EndotheliumIntegration of the Vascular Response (Ascending
Dilatation)
CHAPTER 34Ion channels and Arteriolar Tone 221William F. Jackson
IntroductionIon Channels Expressed in ArteriolesMembrane Potential and Arteriolar Tone at RestIon Channels and VasoconstrictionIon Channels and VasodilationIon Channels and Disease States
CHAPTER 35Roles of Nitric Oxide in the Microcirculation 229Michelle I. Lin and William C. Sessa
IntroductionNO and VasodilationNO and the Homeostasis of the Blood Cell Interaction with
the Vessel WallRole of NO in Regulating Vascular PermeabilityConclusions
CHAPTER 36Rheology of Blood Flow in the Microcirculation 233Herbert H. Lipowsky
IntroductionMicrovascular HematocritApparent ViscosityRed Cell AggregationBlood Cell DeformabilityResistance to Blood Flow in Microvessels
CHAPTER 37Endothelial Ca2+ and Endothelium-DerivedHyperpolarizing Factor (EDHF)-MediatedVasodilatation 239Sean P. Marrelli
The Endothelium as a Modulator of Vascular ToneAn Additional Mechanism of Vasodilatation, EDHFMechanism of EDHF-Mediated VasodilatationRole of KCa Channels in EDHF-Mediated DilationRole of Endothelial [Ca2+]i in EDHF-Mediated
VasodilatationHow Does Elevated Endothelial [Ca2+]i Produce
Vasodilatation?A Relationship between Endothelial Membrane Potential
(Vm) and Endothelial [Ca2+]i?Role of Endothelial [Ca2+]i in EDHF-Mediated Responses
in PathologySummary of Endothelial [Ca2+]i in EDHF-Mediated
Vasodilatation
CHAPTER 38Role of the Endothelial Cell Cytoskeleton in Microvascular Function 247Laura Linz McGillem and Joe G. N. Garcia
IntroductionMicrofilament Cytoskeleton OverviewEndothelial Cell MLCK IsoformRho Family GTPases and the CytoskeletonMicrotubule Cytoskeleton OverviewMicrotubules and Vascular Barrier FunctionMicrotubules and Response to Shear StressMicrotubules and Tube FormationIntermediate Filament Cytoskeleton OverviewMechanical Strain, Shear Stress, and FlowIntermediate Filaments and Microvascular Endothelial
Cell–Cell JunctionsIntermediate Filaments and Microvascular Endothelial
Cell–Matrix JunctionsSummary
CHAPTER 39Microvascular Permeability 255C. C. Michel
IntroductionPermeability CoefficientsPermeability Coefficients of Microvessels in Different
Tissues and Their InterpretationPermeability and Exchange of Fluid and Solute between
Blood and Tissues under Physiological Conditions
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CHAPTER 40TNF-a-Induced Pulmonary Endothelial Permeability: The Role of the Microtubule Cytoskeleton 261Irina Petrache, Anna A. Birukova, and Alexander D. Verin
Endothelial Barrier FunctionTumor Necrosis Factor-aMicrotubulesThe Role of the Mitogen Activated Protein Kinase
(MAPK) Pathway
CHAPTER 41Vasoactive Signals and Pericyte Function in the Retina 265Donald G. Puro
Role of Pericytes in Blood Flow RegulationRegulation of Pericyte ContractilityEffects of Vasoactive Signals on Pericyte PhysiologyPericyte Pathobiology
CHAPTER 42Regulation of MicrovascularHydraulic Conductivity 271Rolando E. Rumbaut and Virginia H. Huxley
IntroductionForces Regulating Transvascular Water MovementPathways for Volume Flux across Microvascular WallsAssessment of Transvascular Water Movement in VivoRegulation of Hydraulic ConductivitySummary
CHAPTER 43The Role of Gap Junctions in the Regulation of Arteriolar Tone 275N. M. Rummery and C. E. Hill
Structure and Regulation of Gap JunctionsExpression of Gap Junctions in Vascular TissueInvolvement of Gap Junctions in Responses Affecting
Arteriolar ToneConclusions
CHAPTER 44Vascular Control Mechanisms in Skeletal Muscle 281Ingrid H. Sarelius
I. Microvascular Network Organization in Skeletal MuscleII. The Cells of the Arteriolar WallIII. Differential Responses of Large versus Small
ArteriolesIV. Metabolic Regulation of Arteriolar ToneV. Integration of Metabolic Response PathwaysVI. Control of Capillary RecruitmentVII. Venular–Arteriolar CommunicationSummary
CHAPTER 45Protein Kinases and MicrovascularPermeability 287Mack H. Wu and Sarah Y. Yuan
Myosin Light-Chain Kinase (MLCK)Protein Kinase C (PKC)cAMP- and cGMP-Dependent Protein Kinases (PKA and
PKG)Mitogen-Activated Protein Kinases (MAPKs)Nonreceptor Protein Tyrosine Kinases (PTKs)Summary
Section E: Transport, Junctions, Adhesion Molecules
CHAPTER 46Vesiculo-vacuolar Organelles Are Permeability Structures in the Endothelium of Normal and Tumor Microvessels 297Ann M. Dvorak and Dian Feng
IntroductionVVOs Are the Major Site of Hyperpermeability of Tumor
Blood VesselsVVO StructureVVO FunctionVVO FormationVVO Fate
CHAPTER 47The Multistep Cascade of Leukocyte Extravasation 303Britta Engelhardt and Dietmar Vestweber
IntroductionThe Multistep ParadigmOutlook
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CHAPTER 48Vascular Endothelial Cadherin and Neutrophil Transmigration 309Bastien Hermant, Marianne Weidenhaupt, Stéphanie Heyraud,and Danielle Gulino-Debrac
IntroductionMarkers Expressed at Endothelial Cell–Cell JunctionsMechanism of Leukocyte DiapedesisConclusions
CHAPTER 49Vascular Gap Junctions 317Michael Koval and Jahar Bhattacharya
IntroductionConnexinsGap Junctional RegulationVascular Connexin ExpressionConnexins and Vascular ToneVascular Connexins in Pathologic ConditionsConclusion
CHAPTER 50Adhesion Molecules and the Recruitment of Leukocytes in Postcapillary Venules 321Klaus Ley
Postcapillary VenulesLeukocytesAdhesion MoleculesPhysiology of Leukocyte–Endothelial InteractionsUnresolved Questions
CHAPTER 51Cell Adhesion Molecules: Structure, Function, Organization and Role in Leukocyte Trafficking through the Lung 327Lina H.K. Lim and Bruce S. Bochner
IntroductionGeneral Dynamic Events Leading to Leukocyte
MigrationEndothelial AMs Involved in Leukocyte TraffickingTissue-Specific Expression of AMs in the Lung
MicrovasculatureSummary
CHAPTER 52The Endothelium from a T-cell Point of View 335Federica Marelli-Berg
Regulation of T-cell Trafficking by the EndotheliumImmunogenicity of the Microvascular EndotheliumTCR-Dependent T-Cell Trafficking
CHAPTER 53Integrins and Formation of the Microvasculature 339Joseph H. McCarty and Richard O. Hynes
IntroductionMicrovascular Integrins and Their Extracellular Matrix
LigandsInterpreting the Conflicting DataCross-talk between Vascular Integrins and Receptor
Tyrosine KinasesThe Role of the ECM in Regulating Vascular Integrin
FunctionsConclusion
CHAPTER 54Platelet Phospholipids Tighten the Vascular Endothelial Barrier 345Fred L. Minnear
Platelets Support the Endothelial BarrierLysophosphatidic Acid (LPA)Sphingosine 1-Phosphate (S1P)Regulation of Vascular Endothelial Permeability and
Proposed Cellular TargetsCell-Signaling PathwaysRac and RhoConclusions and Future Studies
CHAPTER 55Role of Gap Junctions in Capillary-Arteriolar Communication 353Karel Tyml
IntroductionGap Junctions in the MicrovasculatureEvidence for Capillary–Arteriolar CommunicationCommunication along the Microvasculature during
SepsisSummary
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PART IIORGAN MICROVASCULAR ADAPTATIONS
Section A: Cardiology
CHAPTER 56Cardiac Microvasculature 361William C. Aird
IntroductionStructural TopologyRegulation of Coronary FlowThe Endothelium as an Input–Output DeviceApplying the Input–Output Analogy to Cardiac
Microvasculature in HealthApplying the Input–Output Analogy to Cardiac
Microvasculature in DiseaseConclusions
Section B: Central Nervous System and Eye
CHAPTER 57The Vasculature of Choroid 369Imran A. Bhutto and Gerard A. Lutty
Gross AnatomyThe Choroidal Vasculature and Associated StructuresVisualization of the Choroidal VasculaturePhysiologyCell BiologyPathologySummary
CHAPTER 58The Role of the Cytoskeleton in BarrierFunction of the Microvasculature 375Steven M. Dudek and James H. Finigan
IntroductionOverview of the CytoskeletonRegulation of Permeability by the Endothelial Cell
CytoskeletonDifferential Regulation of Permeability in the
Microvasculature
CHAPTER 59Microcirculation of the Brain 381Frank M. Faraci and Donald D. Heistad
Endothelium and the Blood-Brain BarrierEndothelium and Vascular TonePotassium ChannelsEndothelium-Derived Contracting FactorReactive Oxygen and Nitrogen SpeciesAngiotensin II
CHAPTER 60Model Systems for Studying Blood–Brain Barrier Function 385K. L. Hallene, G. Dini, and D. Janigro
Monodimensional Models of the Blood–Brain Barrier:Endothelial Cells
Bidimensional Models of the Blood–Brain Barrier: Co-culture of Endothelial Cells and Glia
Tridimensional Dynamic Models of the Blood–Brain Barrier (Flow-Based)
Cell Lines versus Primary CulturesIn Vitro Models of the Human Blood–Brain BarrierConclusions
CHAPTER 61Adrenomedullin and Blood–Brain Barrier Function 391Béla Kis
AM, a Vasoactive HormoneRole of AM in the MicrocirculationAM Production in the Cerebral MicrocirculationAM Receptors in the Cerebral MicrocirculationRole of AM in Blood–Brain Barrier FunctionsSummary
CHAPTER 62Cerebral Microvascular Blood Oxygenation and Neuronal Activity 395Ute Lindauer
AbstractIntroduction: Definition of the SubjectCerebral Blood Oxygen Tension and Hemoglobin Oxygen
Saturation at RestCerebral Microvascular Blood Flow Changes during
Functional ActivationCerebral Microvascular Blood Oxygenation Changes
during Increased Neuronal ActivitySpatial Resolution of Cerebral Microvascular Blood
Flow and Blood Oxygenation Changes during NeuronalActivation
Cerebral Microvascular Blood Oxygenation Changes during Increased Inhibition or Cortical Deactivation
Summary
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CHAPTER 63The Retina Microvasculature 401Ming Lu and Anthony P. Adamis
AnatomyPhysiologyPathophysiology
CHAPTER 64Nitric Oxide and Blood–Brain Barrier Function 405William G. Mayhan
Concept of a Blood–Brain BarrierNitric Oxide SynthasesRole of Nitric Oxide in Basal Integrity of the Blood–Brain
BarrierRole of Nitric Oxide in Stimuli-Induced Changes in the
Blood–Brain BarrierCellular Mechanisms for the Effects of Nitric Oxide on the
Blood–Brain BarrierSummary and Conclusions
CHAPTER 65Fatty Acids Induce Tight Junctions in Brain Capillary Endothelial Cells 411Kazuo Yamagata, Motoki Tagami, Yasuo Nara, Shingo Itoh,Hidehiko Yokogoshi, and Yukio Yamori
IntroductionOverview: Tight Junction and Fatty AcidsMetabolism and Supply of Polyunsaturated Fatty Acids to
Brain Capillary Endothelial CellsRegulation of Tight Junction Formation by Fatty AcidsConclusion
Section C: Gastrointestinal Tract
CHAPTER 66Microcirculation in Peritoneal Exchange 417Michael F. Flessner
IntroductionDescription of the SystemQuantitative Approach to Peritoneal ExchangePathological States and Alterations in the Peritoneal
Transport SystemIntegration of the Peritoneal Transport System
CHAPTER 67Peritoneal Microvessels and High Peritoneal Solute Transport Rate (PSTR) 429Miwako Numata, Makio Kawakami, Bengt Lindholm, andMasaaki Nakayama
IntroductionPeritoneal Microvascular ArchitectureThree-Pore TheoryEstimation of Peritoneal Transport RateThe Relationship between PSTR and Alterations of
Peritoneal Microvessels in PD PatientsCandidate Molecules Related to Angiogenesis and/or
DilatationVasculopathy
CHAPTER 68The Gastrointestinal Microcirculation 433Thorsten Vowinkel and D. Neil Granger
Gastric MicrocirculationIntestinal MicrocirculationPathophysiology of the GI Circulation
Section D: Hematopoietic System
CHAPTER 69The Bone Marrow Vasculature 439Jorge Domenech and Pierre Charbord
Hematopoiesis and Its MicroenvironmentThe Vascular NetworkThe BM Blood FlowThe Marrow SinusPathology
Section E: Kidney
CHAPTER 70Renal Medullary Microcirculation 447Thomas L. Pallone, Janos Pittner, and Whaseon Lee-Kwon
IntroductionTubular Vascular Relationships in the Renal MedullaCountercurrent Exchange and Transport PropertiesVasoactivity of DVRMedullary Oxygen Tension and Perfusion of the MedullaThe Importance of Medullary Blood Flow and Nitric
Oxide in Hypertension
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CHAPTER 71Renal Cortical Microcirculation 455William J. Welch
IntroductionControl of Renal Cortical Microvascular ResistanceVascular Resistance in Transplanted KidneysSummary
Section F: Liver
CHAPTER 72Hepatic Microvascular Responses to Inflammation 465Claudine S. Bonder and Paul Kubes
The Hepatic Microvascular SystemLiver ConstitutionMediators of Hepatic InflammationCellular Adhesion MoleculesConclusion
CHAPTER 73Liver Microcirculation 471Robert S. McCuskey
Blood Supply to the LiverMicrovascular Functional UnitsHepatic Microvascular SystemStructure and Function of Hepatic SinusoidsPathophysiology of the Hepatic Microcirculation
CHAPTER 74Gaseous Signal Transduction in Microcirculation 477Makoto Suematsu and Nobuhito Goda
Signal Transduction by O2
Microvascular actions of CO
Section G: Lung
CHAPTER 75Lung Endothelial Cell Heterogeneity and the Microvasculature 485Abu-Bakr Al-Mehdi, Kane L. Schaphorst, and Troy Stevens
AbstractIntroductionEndothelial Cell Heterogeneity in the Pulmonary
CirculationConclusion
CHAPTER 76Lung Edema and MicrovascularPermeability 491Richard D. Minshall and Stephen M. Vogel
IntroductionStarling Forces Underlying Pulmonary Edema Formation,
Accumulation, and ResolutionCellular Mechanisms of Permeability Edema: Endothelial
Barrier DysfunctionSummary
CHAPTER 77Forms of Reserve in the Pulmonary Capillary Bed 497Wiltz W. Wagner, Jr., and Robert G. Presson, Jr.
Capillary Transit TimeDistentionRecruitment
CHAPTER 78Fragility of Pulmonary Capillaries 505John B. West
IntroductionPulmonary versus Systemic CapillariesStructure of Pulmonary CapillariesStrength of Pulmonary CapillariesMechanical Stresses in the Walls of Pulmonary
CapillariesStress Failure in the Wall of the Pulmonary CapillaryPhysiological Conditions Associated with Stress Failure of
Pulmonary CapillariesPathological Conditions Causing Stress FailureRegulation of the Structure of Pulmonary Capillaries
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Section H: Lymphatics
CHAPTER 79Lymphatic Endothelial Cells: Heterogeneity from Blood Endothelium and Unique Properties in Health and Disease 513J. Steven Alexander
Lymphatic versus Blood Endothelial BiologyUnique Structural/Functional Markers: Lymphatic versus
BECJunctions and Solute Barrier Function in Blood and
Lymphatic VesselsEndothelial-Cell Adhesion Molecules in BECs versus
LECsChemokines Released by LECs and BECsLymphatic DevelopmentLymphatics in Disease: Lymphedema and CancerSummary
CHAPTER 80Lymphocyte Interaction with Microvascular Endothelium 517Sirpa Jalkanen and Marko Salmi
AbstractPhysiological Lymphocyte RecirculationInflammation-Induced ChangesMolecular Events in Lymphocyte–Endothelial Cell
InteractionImportance of the Endothelial Homing-Associated
MoleculesEndothelial Homing-Associated Molecules as Drug Targets
CHAPTER 81The Lymphatic System 523Michael S. Pepper
Growth and Structure of the Lymphatic TreeLymphatic Endothelial CellsA Renewed Perspective on the Physiopathology of the
Lymphatic SystemSummary and Perspectives
CHAPTER 82Foundations of Microlymphatic Function 529Geert W. Schmid-Schönbein
IntroductionStructure of MicrolymphaticsLymphatic EndotheliumLymphatic Endothelial JunctionsMechanisms for Periodic Compression of Initial
LymphaticsLymph Fluid Collection and TransportLymphatic Fluid PressuresLymphatic AngiogenesisLymphatics in Tumors
CHAPTER 83Morphology and Physiology of Lymphatic Endothelial Cells 535H. Zöltzer
IntroductionHistoryThe Endothelium of the Initial LymphaticThe Endothelium of the PrecollectorsThe Endothelium of the Collectors and Lymphatic Stem
VesselsThe Endothelium in the Lymph Nodes
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VOLUME 2
Foreword I by Shu Chien vForeword II by Bruce Zetter viiIntroduction ixEditorial Board Members xiiiContributors xv
Section I: Pancreas
CHAPTER 84Pancreatic Microcirculation in Health and Disease 547Leif Jansson, Arne Andersson, Örjan Källskog, and Per-Ola Carlsson
IntroductionNormal PancreasAdaptations to Functional DemandsAcute PancreatitisChronic PancreatitisPancreatic CancerDiabetes MellitusConclusions
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Section J: Skeletal Muscle
CHAPTER 85Exercise and Skeletal Muscle Circulation 553Jeffrey L. Jasperse and M. Harold Laughlin
IntroductionHeterogeneity of Skeletal Muscle Blood Flow during
ExerciseMechanisms Determining Blood Flow DistributionIntegration/Conclusion
Section K: Skin
CHAPTER 86Vascular Responses in Human Skin 565Geraldine F. Clough and Martin K. Church
Structure and Function of the Cutaneous MicrovasculatureTechniques to Assess Cutaneous Microvascular Function in
VivoVascular Responses in Dermal InflammationConcluding Remarks
Section L: Reproductive Systems
CHAPTER 87Vascular Transformation of Placental Cytotrophoblasts 573Susan J. Fisher
Morphological Aspects of Human PlacentationMolecular Regulators of CTB PseudovasculogenesisPhysiological Regulators of CTB PseudovasculogenesisPre-eclampsia Is Associated with Defects in CTB
PseudovasculogenesisConclusions
CHAPTER 88The Microvasculature of the Ovary 579Lawrence P. Reynolds, Anna T. Grazul-Bilska, and Dale A. Redmer
General Aspects of Ovarian FunctionThe Ovarian MicrovasculatureAngiogenesis in the Ovary
CHAPTER 89The Microvasculature of the Endometrium 587Robert D. Koos and L. Christie Rockwell
IntroductionAnatomy of the Endometrial MicrovasculatureMode of Endometrial AngiogenesisFactors Regulating Endometrial AngiogenesisRole of the Endometrial Vasculature in MenstruationCyclic Changes in Endometrial Microvascular
PermeabilityStructural Changes in the Endometrial Microvasculature
Associated with ImplantationThe Endometrial Vasculature and PregnancyThe Endometrial Vasculature and Uterine PathologiesSummary and Conclusion
CHAPTER 90The Vasculature of the Normal Mammary Gland: HIF-1-Independent Expansion and Regression 595Tiffany N. Seagroves and Randall S. Johnson
IntroductionSummary and Future Directions
PART IIIPATHOLOGY
Section A: Alzheimer’s Disease
CHAPTER 91Alzheimer’s Disease and the Microcirculation 605William A. Banks, Naoko Nonaka, Susan A. Farr, and John E. Morley
Perturbances in Microvascular Circulation and EndothelialCell Function
Altered Permeability of the Blood–Brain BarrierTransport of Amyloid Beta ProteinConclusions
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Section B: Acute Respiratory Distress Syndrome
CHAPTER 92Acute Respiratory Distress Syndrome (ARDS) 611Robert H. Demling
DefinitionIncidence and OutcomePathogenesisPathophysiology and CourseTreatmentSummary
Section C: Arthritis
CHAPTER 93The Role of the Microvasculature in the Pathophysiology of Rheumatoid Arthritis 619Ewa Paleolog
IntroductionThe Pathogenesis of Rheumatoid ArthritisWhy Is the Microvasculature Important in RA?Insights from Clinical Trials of Anti-TNFa BiologicalsVascular Endothelium: A Possible Therapeutic Target in
RA?Concluding Remarks
Section D: Blood, Thrombosis and Homeostasis
Hemoglobin-Induced Microvascular Dysfunction
CHAPTER 94Review Hemoglobin-Induced Microvascular Dysfunction 629Ann L. Baldwin
IntroductionProblems Encountered with Hemoglobin-based Blood
Substitutes during TrialsProblems with Hemoglobin-based Blood Substitutes in the
MicrocirculationFuture Possibilities
CHAPTER 95Determinants of Platelet Glycoprotein Ib-IX-V Mediated MicrovascularHemostasis: Are They Different from Those Regulating Thrombosis? 635Michael H. Kroll and Shuju Feng
IntroductionMolecular Effectors of Platelet-Mediated Hemostasis and
ThrombosisClinical Models That Separate GpIb-IX-V Mediated
Thrombosis from HemostasisSummary and Conclusions
CHAPTER 96Complement 643Francis D. Moore, Jr.
IntroductionComplement ActivationMembrane Attack ComplexClinical Assessment of Complement ActivationIntrinsic Regulation of Complement ActivationInteractions between Leukocytes and ComplementComplement Deficiency StatesComplement InhibitorsClinical Injury and Complement ActivationSummary
CHAPTER 97Regulation of Microcirculation by Antithrombin: Molecular Mechanism(s) and Possible Therapeutic Applications 653Kenji Okajima
Anticoagulant activity of ATAnti-inflammatory Activity of ATMolecular Mechanism(s) of the AT-Induced Increase in
Endothelial Production of PGI2Roles of Anti-inflammation and Anticoagulation by AT in
Regulation of MicrocirculationPossible Therapeutic Applications of AT for Conclusions and Perspectives
Section E: Coronary Slow Flow
CHAPTER 98The Coronary Slow Flow Phenomenon 661John F. Beltrame
DefinitionAngiographic FeaturesClinical FeaturesPathophysiological MechanismsTherapeutic ConsiderationsSynopsis
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Section F: Diabetes
CHAPTER 99Endothelins and MicrovascularEndothelial Responses in Diabetes 671Subrata Chakrabarti and Zia Ali Khan
EndothelinsMechanism of ET Alteration in DiabetesETs and Microcirculatory Flow AlterationsEndothelins in Microvascular Endothelial DysfunctionEndothelins in Organ-Specific Microvascular Alterations in
DiabetesConcluding Remarks
CHAPTER 100Pericytes and Diabetic Retinopathy 677Hans-Peter Hammes
General RemarksIntroductionPericytes in Vascular Biology: A Brief OverviewThe Natural Course of Human Diabetic RetinopathyLessons from Genetically Modified Diabetic AnimalsLinking Biochemistry to Cell Biology of Diabetic
Retinopathy: The Unifying Hypothesis
CHAPTER 101Von Willebrand Factor Diabetes and Endothelial Dysfunction 683Alberto Verrotti, Rita Greco, Guido Morgese, and Francesco Chiarelli
IntroductionPhysiopathology of Vascular EndotheliumHyperglycemiaPolyol Pathway and Protein Kinase C ActivationAdvanced Glycosylation End Products (AGEs)Oxidative StressCoagulation Cascade
Section G: Hemorrhagic Fever Viruses
CHAPTER 102The Vascular Endothelium as a Target for the Hemorrhagic Fever Viruses 689Silvia Montaner and J. Silvio Gutkind
AbstractHemorrhagic Fever VirusesInfection with Filoviruses: Ebola and MarburgThe Role of the Vascular Endothelium in Ebola
PathogenesisEbola Pathogenic GenesModels to Study the Pathogenesis of Ebola VirusConclusion
Section H: Hypercholesterolemia
CHAPTER 103Microvascular Responses to Hypercholesterolemia 697Karen Y. Stokes and D. Neil Granger
IntroductionHypercholesterolemia and ArteriolesHypercholesterolemia and CapillariesPostcapillary Venules and HypercholesterolemiaExaggerated Inflammatory Responses during
HypercholesterolemiaRelevance of Hypercholesterolemia-Induced Microvascular
Responses to Atherosclerosis
Section I: Hypertension
CHAPTER 104Arteriolar Responses to Arterial Hypertension 705Julian H. Lombard
Importance of the Arterioles in HypertensionEnhanced Sensitivity of Arterioles to Vasoconstrictor
Stimuli in HypertensionImpaired Relaxation of Arterioles to Vasodilator StimuliStructural Alterations in Arterioles during HypertensionArteriolar RarefactionOxidative Stress and Arteriolar Function in HypertensionDietary Salt Intake and Arteriolar FunctionInfluence of Gender on Arteriolar Function in
Hypertension
CHAPTER 105Capillary and Venular Responses to Arterial Hypertension 713Geert W. Schmid-Schönbein
IntroductionStructure of MicrolymphaticsLymphatic EndotheliumLymphatic Endothelial JunctionsLymph Fluid Collection and TransportLymphatic Fluid PressuresLymphatic AngiogenesisLymphatics in Tumors
Contents xxxix
Section J: Inflammation
CHAPTER 106Free Radicals and Lipid Signaling inMicrovascular Endothelial Cells 721Peter B. Anning and Valerie B. O’Donnell
IntroductionProstaglandin H synthases-1 and -2 in ECsLipoxygenases in ECsCYP Enzymes in ECsGeneration of Free Radical Species by PGHS or LOX and
CYPRegulation of PGHS, LOX, and CYP by Reactive Oxygen
and Nitrogen SpeciesConclusionsSummary
CHAPTER 107Eicosanoids 727Monica M. Bertagnolli
Introduction: History and DefinitionsConverting Membrane Components into Signaling
MoleculesKeeping the Balance: Implications for Health and DiseaseActivity and Specificity of Inhibitors of Arachidonic Acid
MetabolismConclusion
CHAPTER 108Sepsis and the Microvasculature 735Alpha A. Fowler, III
Sepsis EpidemiologyNitric Oxide Induces Microcirculatory DysfunctionLipopolysaccharide Entry into the Circulation and
Cytokine Transcription Promote Microvascular Dysfunction in Sepsis
Apoptosis of Endothelium in SepsisAdhesion Molecules Orchestrate Neutrophil SequestrationSepsis Induces Microvascular Thrombosis and Produces
Poor Clinical OutcomesConclusions
CHAPTER 109Interaction of C1q with the Endothelium: Relevance to Inflammation 741Berhane Ghebrehiwet and Ellinor I. B. Peerschke
The Endothelium and InflammationThe Endothelial Cell Surface and C1q ReceptorsC1q-Mediated Endothelial Cell Responses: Role of C1q
and HKRegulation of the Endothelium
CHAPTER 110The Microvasculature in Inflammatory Bowel Disease 745Ossama A. Hatoum and David G. Binion
IntroductionThe Role of the Microvasculature and Endothelial–
Leukocyte Interaction in Chronic Intestinal Inflammation
The Role of Microvascular Dysfunction and TissueIschemia in Chronic Intestinal Inflammation
Summary
CHAPTER 111Pathophysiology of Edema Formation 749Dan D. Hershko and Michael M. Krausz
Hemodynamic Aspects of Edema FormationInflammatory Aspects of Edema FormationIdiopathic Edema
CHAPTER 112Endothelium in Malarial Infection: More Than an Innocent Bystander 755May Ho, Bryan G. Yipp, and Stephen M. Robbins
IntroductionPlasmodium falciparum MalariaCytoadherenceCD36PfEMP1 and Recombinant 179 PeptidesCD36-Mediated Intracellular SignalingCD36 Signaling via Src-family Kinases Modulates IRBC
AdhesionDownstream Signaling EventsPossible Role of Other Receptor MoleculesOther Signaling Events Triggered by P. falciparum
CHAPTER 113Ischemia–Reperfusion Injury 761Shahrul I. Ibrahim, Rodney K. Chan, and Herbert B. Hechtman
IntroductionEvents Occurring during Ischemia–ReperfusionOverview of InflammationNeutrophils and Free Radicals in Ischemia–Reperfusion.Overview of the Complement SystemComplement Activation by Immune Complexes during
ReperfusionBinding of the Ischemia Antigen by Natural AntibodiesCurrent ControversiesClinical Use of Complement Inhibitors in Reperfusion
InjuryThe Future: Mast Cells and Substance PConclusion
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CHAPTER 114Endothelial Xanthine Oxidoreductase and Vascular Disease 769Usamah S. Kayyali and Paul M. Hassoun
IntroductionBiology and Function of Xanthine OxidoreductaseXanthine Oxidoreductase in Endothelial CellsRegulation of Xanthine Oxidoreductase in Health and
DiseaseRelation to Other Reactive Oxygen ProducersXOR and Models of InjuryXanthine Oxidoreductase: An Enigmatic Enzyme
CHAPTER 115Antecedent Ethanol Ingestion Prevents Postischemic MicrovascularDysfunction 777Ronald J. Korthuis
IntroductionMicrovascular Consequences of Ischemia–ReperfusionAnti-inflammatory Effects Induced by Ethanol IngestionSignaling Mechanisms That Induce the Adaptive
Transformation to a Protected Phenotype in the Microcirculation after Ethanol Ingestion
P-Selectin Expression as a Molecular End Target ofEthanol Preconditioning
CHAPTER 116Microvascular Dysfunction in Inflammatory Bowel Disease 783F. Stephen Laroux and Matthew B. Grisham
IntroductionOrganization of the Intestinal and Colonic
Microcirculation: Anatomical and Functional Considerations
Arteriolar and Capillary Alterations Associated with IBDVenular Alterations in IBD
CHAPTER 117Analytical Approaches to Leukocyte–Endothelium Interactions 791Lance L. Munn
IntroductionMarginationContactRollingArrestConclusion
CHAPTER 118Microvascular Responses to Eicosanoids 795Mauro Perretti and Derek W. Gilroy
Arachidonic Acid MetabolismProstaglandinsLeukotrienesLipoxins
CHAPTER 119Oxidants and Vascular Signaling Mechanisms 801Michael S. Wolin
Importance of Oxidant Signaling Mechanisms in theMicrocirculation
Sources of Oxidant SpeciesMechanisms of Interactions of Oxidant Species with
Vascular Signaling SystemsPhysiological Importance of Vascular Oxidant SignalingRoles of Oxidant Signaling Mechanisms in Microvascular
Function
CHAPTER 120Reactive Oxygen Species and The Microcirculation 805John G. Wood and Norberto C. Gonzalez
Microvascular Responses to Oxidative StressSources of ROSEndogenous Defenses against ROSIschemia/Reperfusion-Induced Microvascular
InflammationMicrovascular Responses to Systemic HypoxiaSummary
Section K: Immunology
CHAPTER 121Autoantibodies to Endothelial Cells 813Jeremy D. Pearson and Sarah E. Riley
Autoimmune Diseases and AutoantibodiesAnti-endothelial Cell Autoantibodies (AECAs)Potential Pathogenic Roles for AECAsConclusions
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Section L: Kidney Transplant Rejection
CHAPTER 122Microvasculature in Kidney Transplant Rejection 819Vladimir Savransky, Mark Haas, and Hamid Rabb
Basics Immunobiology of Kidney Allograft RejectionMicrovasculature and Renal Transplant Rejection
Section M: Leak Syndrome
CHAPTER 123Sepsis-Induced MicrovascularLeak Syndrome 827Gernot Marx and Martin Leuwer
IntroductionPathogenesisClinicalDrug TherapyConclusion
Section N: Lung Injury
CHAPTER 124Microvascular Responses to Acute Lung Injury 835Kazunori Murakami and Daniel L. Traber
IntroductionPulmonary Circulation Is UniqueNitric Oxide and Superoxide Play a RoleNeutrophil Elastase Injures Pulmonary Endothelial CellsWhat Factors Increase the Pulmonary Transvascular Fluid
Flux?Airway Obstruction Plays Role in ALINeutrophils and Pulmonary Endothelial Cells Are Targets
to Treat ALIEndothelial Cell Injury Induces Microcirculation
DisturbancesConclusion
Section O: Organ Transplantation
CHAPTER 125Microvascular Responses to Organ Transplantation 843Michael D. Menger and Brigitte Vollmar
IntroductionDonor Organ ConditionsOrgan Donor ConditionsDonor Organ ConditionsOrgan Preservation ProceduresSurgical Transplant ProceduresTransplant Reperfusion-Associated InflammationConclusions and Clinical Perspectives
Section P: Periodontal Disease
CHAPTER 126The Pathobiology of the Periodontium:Insights into Vascular Dysfunction and Acceleration of Atherosclerosis 851Evanthia Lalla, Panos N. Papapanou, Ira B. Lamster, and Ann Marie Schmidt
Periodontal Disease, Vascular Inflammation, and Dysfunction
A Murine Model of Accelerated Atherosclerosis in MiceInfected with a Periodontal Pathogen
Other Systemic Diseases and Acceleration of Microvascular Dysfunction and Atherosclerosis
“Closing the Loop” on RAGE, Periodontal Disease, andVascular Inflammation
CHAPTER 127The Possible Roles of Vascular EndothelialGrowth Factor in Periodontal Disease 857Kanyarat Suthin, Miho Machigashira, and Yuichi Izumi
DefinitionIntroductionVEGF FamilyVEGF ReceptorsSynthesis and Regulation of VEGFRole in Disease ProcessesRole in Periodontal DiseaseTherapeutic ApplicationsFuture Perspectives
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Section Q: Pollutants
CHAPTER 128Microvascular Responses to Cigarette Smoke 863Hans-Anton Lehr
Morphological Aspects of Cigarette Smoke-InducedMicrovascular Dysfunction
Functional Aspects of Cigarette Smoke-Induced Microvascular Dysfunction
Cellular Targets of Cigarette Smoke-InducedMicrovascular Dysfunction
Consequences of Cigarette Smoke-Induced MicrovascularDysfunction
Prevention of Cigarette Smoke-Induced MicrovascularDysfunction
CHAPTER 129Effects of Cigarette Smoke on RheologicalProperties of Leukocytes Influencing TheirPassage through the Microvasculature 869G. B. Nash and W. MacNee
IntroductionEffects of Cigarette Smoking on Behavior of Leukocytes
in the MicrocirculationEffects of Cigarette Smoke on Leukocytes: Changes in
Resistance to FlowEffects of Cigarette Smoke on Leukocyte AdhesionConclusions
CHAPTER 130Pulmonary Response to Environmental and Occupational Pollutants 877Nicola Verna and Mario Di Gioacchino
IntroductionIrritant ReactionsImmunologic ReactionsFibrogenic ReactionsParticle Problem and Its Multiple Mechanisms
Section R: Pre-eclampsia
CHAPTER 131Microvascular Permeability in Pre-eclampsia 889Nick Anim-Nyame, John Gamble, and Philip J. Steer
IntroductionVolume Homeostasis in Normal PregnancyMechanisms for Plasma Volume Changes in Normal
PregnancyTranscapillary Forces and Microvascular Permeability in
Normal PregnancyMicrovascular Permeability in Pre-eclampsiaFuture ResearchSummary
Section S: Wound Healing
CHAPTER 132Wound Healing: An Orchestration ofHumoral and Cellular Forces 897Rodney K. Chan, Perry H. Liu, and Dennis P. Orgill
IntroductionWound Healing CascadeGrowth Factors in Wound HealingWound ReepithelializationWound Healing and the Immune SystemClinical Trials in Wound Healing Using Growth FactorsFuture Directions: Involvement of the Nervous SystemVacuum-Assisted Wound ClosureConclusion
CHAPTER 133Microvascular repair 903Jamie Y. Jeremy and Michael R. Dashwood,
IntroductionThe Diversity of Microvascular DamageAngiogenesisThe Cell Cycle and ProliferationMigrationMatrix and Matrix MetalloproteinasesTriggers for Vascular Repair in Wound HealingFactors Influencing AngiogenesisReactive Oxygen Species and AngiogenesisAnti-angiogenic FactorsAngiogenesis in Vein Grafts: Impact of the External Stent.Risk Factors for Impairment of Microvascular Repair.Concluding Remarks
Contents xliii
Section T: Sclerosis
CHAPTER 134The Role of Microvascular Pericytes in Systemic Sclerosis 915Vineeth Rajkumar, David Abraham, and Carol Black
IntroductionMicrovascular Abnormalities in SScMicrovascular PericytesRole of Pericytes in FibrosisPericytes as Tissue-Specific Mesenchymal Stem CellsConcluding Remarks
Section U: Skin
CHAPTER 135Impaired Skin Microcirculatory Function in Human Obesity 921Alexei V. Agapitov and William G. Haynes
Skin Microvasculature and Techniques for Measuring SkinBlood Flow
Importance of Skin Microvasculature and Alterations ofSkin Microcirculation in Obesity
Potential Mechanisms Responsible for Deficient SkinVasodilatation to Mental Stress in Obesity
Conclusions
CHAPTER 136Cutaneous Microcirculation in Patients with Scleroderma 925Michael Junger and Anja Schlez
CHAPTER 137Angiogenic Diseases of the Skin 929Rainer Kunstfeld and Michael Detmar
Structure and Function of Cutaneous Blood VesselsMolecular Control of Skin AngiogenesisAngiogenesis in Skin Diseases
CHAPTER 138Skin Microcirculation in the Elderly 933Marco Rossi and Carlo Palombo
IntroductionSkin Microcirculation in the ElderlyClinical Implications and Perspectives
Section V: Tumors
CHAPTER 139Tumor Growth Patterns and Angiogenesis 941Cecile G. Colpaert and Peter B. Vermeulen
Growth Patterns and Angiogenesis in Primary Breast Cancer
Growth Patterns and Angiogenesis in Cutaneous BreastCancer Deposits
Growth Patterns and Angiogenesis in Liver MetastasesGrowth Patterns and Angiogenesis in Primary Lung CancerConclusion
CHAPTER 140Breast Cancer Resistance Protein in Microvessel Endothelium 947Hiran C. Cooray and Margery A. Barrand
IntroductionABC TransportersABC Transporters Associated with Multidrug ResistanceTissue Distribution of BCRR Compared to Other
Multidrug Transporters
CHAPTER 141Tumor vs Normal Microvasculature 955Moritz A. Konerding
Introduction and DefinitionsStructural Differences between Tumor and Normal
MicrovasculatureArchitectural Differences between Normal and Tumor
Microvasculature
CHAPTER 142Endothelial Cell Heterogeneity: Targeting the Tumor Tasculature 961Robert R. Langley
IntroductionAngiogenesisRole of the Microenvironment and AngiogenesisTargeting Angiogenesis in TumorsTumor VasculogenesisConclusion
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CHAPTER 143A Metronomic Approach to Antiangiogenesis 969Raffaele Longo and Giampietro Gasparini
IntroductionMetronomic ChemotherapyExperimental SstudiesClinical StudiesFuture Directions and Open Questions
CHAPTER 144Platelet–Endothelial Interaction in Tumor Angiogenesis 975Philipp C. Manegold and Marc Dellian
Physiology of Platelet–Endothelial InteractionPlatelet–Endothelial Interaction in Tumor AngiogenesisPlatelets Are Potentially Involved in Tumor AngiogenesisPlatelet–Endothelial Interaction Following Endothelial
StimulationConclusions
CHAPTER 145Von Hippel–Lindau Disease: Role ofMicrovasculature in Development of the Syndrome 981David R. Mole and Peter J. Ratcliffe
The von Hippel–Lindau Hereditary Cancer SyndromeThe VHL Protein (pVHL)pVHL and Oxygen SensingHypoxia-Inducible Factor and AngiogenesisHIF and Tumorigenesis
CHAPTER 146Angiostatin Inhibits Signaling in Endothelial and Smooth-Muscle Cells 989David C. Sane
OverviewAngiostatin: An Inhibitor of AngiogenesisCellular Mechanisms for the Antiangiogenic Activity of
AngiostatinProposed Molecular Targets of AngiostatinNontumor Effects of AngiostatinSummary
CHAPTER 147Endothelial Cell Transformation by the Kaposi’s Sarcoma–Associated Herpesvirus/Human Herpesvirus-8 993Akrit Sodhi and J. Silvio Gutkind
IntroductionKaposi’s Sarcoma: A Disease in Search of a CauseKaposi’s Sarcoma–Associated Herpesvirus (KSHV or
HHV8)KSHV Latent Genes and the Promotion of Cell
Proliferation and SurvivalKSHV Lytic Genes and Paracrine NeoplasiaTriggering Kaposi’s SarcomagenesisConclusion
CHAPTER 148Endothelial Cells in Kawasaki Disease 999Seiichiro Takeshita and Keigo Nakatani
Pathological FindingsImmunological AbnormalitiesImpaired EC FunctionOther FindingsTherapy for KD Vasculitis
CHAPTER 149Response of Colon Carcinoma Cells to Proinflammatory Cytokines 1003M. Ten Kate and C.H.J. Van Eijck
IntroductionProinflammatory CytokinesEndothelial CellsIn Vitro StudiesIn Vivo StudiesAdhesion MoleculesDiscussion
Section W: Vasculitis
CHAPTER 150Vasculitis 1011Ross Milner and Robert B. Smith, III
AbstractIntroductionCommon VasculitidesImmunologic Mechanisms of DiseaseConclusions
Contents xlv
PART IVTHERAPY
Section A: Hemorrhagic Shock
CHAPTER 151The Effect of Fluid Treatment on theMicrovasculature in Uncontrolled Hemorrhagic Shock 1021Michael M. Krausz
Conclusion
Section B: Preconditioning
CHAPTER 152Mechanisms Involved in Delayed Preconditioning: Initiating, Signaling and Effector Components 1027Tao Rui, Gediminas Cepinskas, and Peter R. Kvietys
IntroductionInitiating MoleculesSignaling MoleculesEffector MoleculesSummary
Section C: Statins
CHAPTER 153Statins and the Microvasculature 1035Reda E. Girgis and Jeffrey R. Jacobson
IntroductionMechanisms of ActionEffects of Statins on the MicrovasculatureStatins as AntioxidantsEffects on Other Vasoactive MediatorsRegulation of the Endothelial Cytoskeleton by StatinsStatin Effects on Vascular Wall Cell Proliferation and
SurvivalAnti-inflammatory Effects of StatinsAntithrombotic Properties of StatinsPotential Clinical Applications of Statins Targeting the
MicrovasculaturePharmacokinetic ConsiderationsConclusion
Section D: Therapeutic Angiogenesis
CHAPTER 154Therapeutic Angiogenesis 1045Michael Simons and Mark J. Post
IntroductionBiology of AngiogenesisAngiogenic Growth FactorsTherapeutic Applications of Angiogenesis ConceptsAssessment of Current ExperienceSummary
Section E: Vascular Endothelium
CHAPTER 155Delivery of Therapeutic and Genetic Materials to Vascular Endothelium 1053Vladimir R. Muzykantov and Sergei M. Danilov
IntroductionMeans for Improvement of Pharmacokinetics and Vascular
Delivery of DrugsPassive Drug Delivery to MicrovasculatureTargeted Drug Delivery to Endothelial Surface
DeterminantsPanendothelial Surface Determinants Candidates for
TargetingTargeting Specific Vascular AreasTargeting of Genetic Materials and Viruses to Endothelial
CellsConclusion
PART VNEW RESEARCH MODES AND PROCEDURES
Section A: DNA Microarray
CHAPTER 156The Identification of Cell Type–Specific Transcripts by DNA Microarray Analysis 1065Andrew Leask
IntroductionBackgroundThe Gene ChipDetection of Genes on the ChipData AnalysisLimitations of the TechnologyThe Use of Arrays to Study the VasculatureFunctionalityConclusion
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CHAPTER 157Gene Expression Profiling of HumanEndothelial Cells by DNA Microarray and SAGE 1069Shui Qing Ye, Shwu-Fan Ma, Dmitry Grigoryev, Mohan Parigi,and William L. Shao
IntroductionDNA Microarray and SAGE TechnologiesApplication of DNA Microarray and SAGE into the Gene
Expression Profiling of Endothelial CellsFuture Perspectives
Section B: Engineered Tissue
CHAPTER 158Angiogenesis of Engineered Tissue 1083Craig Neville and Joseph P. Vacanti
IntroductionBioengineered TissueDelivery of Angiogenic FactorsFabrication of Microvascular Structures
CHAPTER 159Engineering of Blood Vessels 1087Joe Tien, Andrew P. Golden, and Min D. Tang
IntroductionEngineered ArteriesEngineered Microvascular NetworksFuture Directions
CHAPTER 160Blood Substitutes’ Efficacy: Microvascular and Theological Determinants 1095Amy G. Tsai, Pedro Cabrales, Hiromi Sakai and Marcos Intaglietta
The Design of an Efficacious Oxygen-Carrying PlasmaExpander
The Role of Viscosity in Oxygen TransportCounterintuitive Rheological FindingsHemodilution, Blood Viscosity, and VasoactivityThe Vasoconstrictive Effect of HemoglobinOptimal Oxygen Disassociation PropertiesOxygen-Carrying CapacityColloid Osmotic PressureSynthesis of an Effective Oxygen-Carrying Plasma
ExpanderExperimental EvidenceSummary and Conclusions
Section C: Endothelial Biomarker
CHAPTER 161N (Carboxymethyl)lysine as a Biomarkerfor Microvascular Complications 1107Jean-Luc Wautier and Marie-Paule Wautier
IntroductionBiochemistry of CarboxymethyllysineCML and Vascular Cell PathologyCML in Diabetes Mellitus, Aging, and Renal FailureCML and Microvascular Complications
Section D: Knockout/transgenic Models
CHAPTER 162Knockout Mouse Models Have ProvidedInvaluable Insights into MicrovascularDevelopment and Functions 1113Kristofer Rubin, Alexei V. Salnikov, and Christian Sundberg
IntroductionNull Mutants That Affect the Development of the
Microvascular UnitSummary
Section E: Mathematical Models
CHAPTER 163Mathematical Models of Angiogenesis 1121James W. Baish
DefinitionIntroductionConceptual FrameworkPhysical PrinciplesExamplesFuture Directions
CHAPTER 164Mathematical and Computational Models of the Microcirculation 1127Aleksander S. Popel
IntroductionModels of Microvascular Blood FlowModels of Microvascular Transport of Oxygen and
Nitric OxideModels of Regulation of Microvascular Blood FlowSummary and Future Studies
Contents xlvii
Section F: Proteomics
CHAPTER 165Proteomics of the Microvasculature 1137Emma McGregor and Michael J. Dunn
IntroductionTwo-Dimensional Gel ElectrophoresisProtein DetectionProtein IdentificationVessel Proteomics
CHAPTER 166Proteomics and the Microvasculature 1143John H. Stone and Emanuel F. Petricoin
AbstractIntroduction“Classic” ProteomicsTwo-Dimensional Gel ElectrophoresisNewer Approaches to Differential DisplayMass SpectrometryTandem Mass SpectrometryApproaches to Protein IdentificationProtein Microarrays
Section G: Stem Cells
CHAPTER 167The Therapeutic Promise of Endothelial Stem Cells 1155Denis English, Kevin Harvey, and Ursula Gehling
Definition of the SubjectThe Essence of the Vascular SystemThe Diverse EndotheliumAdult Endothelial Progenitor CellsEmbryonic Vascular Progenitor CellsStem Cell TherapySummary and Outlook
Index 1165
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