aterosclerosi atherosclerosis is an inflammatory disease characterized by intense immunological...

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Page 1: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 2: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

ATEROSCLEROSI

Page 3: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide.

Atherosclerosis involves the formation in the arteries of lesions that are characterized by inflammation, lipid accumulation, cell death and fibrosis. Over time, these lesions, which are known as atherosclerotic plaques, mature and gain new characteristics.

HANSON AND LIBBYNature Reviews Immunology 6:508-519, 2006

Page 4: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 5: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

FATTORI DI RISCHIO E TEORIA DELLA REAZIONE AL DANNO

Page 6: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 7: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 8: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 9: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

von Andrian UH and Mackay CR N Engl J Med 343, 1020, 2000

L ’inattivazione di geni codificanti per proteine implicate nel reclutamento monocitario riduce lo sviluppo diLesioni ateroscelrotiche in topi con inattivazione genica di APOE o LDL-R

X X XX

X

MCP-1

CX3C, CXCR2, CCR2 chain

Page 10: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 11: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 12: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

Pathogen-associated molecular patternsPathogen-associated molecular patterns Damage-associated molecular patternsDamage-associated molecular patterns

Nuclear proteins:-HMGB1 (high mobility group box1 protein)-Histones-Cytosolic proteins: heat shock proteins

Nuclear proteins:-HMGB1 (high mobility group box1 protein)-Histones-Cytosolic proteins: heat shock proteins

Page 13: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 14: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide
Page 15: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

Formazione di NETs Danno endoteliale

In seguito all’esposizione ad endotossine le piastrine interagiscono (???) con PMNinducendo la formazione di NETs

TLR4

batteri

Page 16: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide

Inizio lesione: eliminazione“cause”

APPROCCI PREVENTIVI E TERAPEUTICI

Progressione della placca: inibizioneformazione di placca “instabile”

Complicanze trombotiche: riduzione fattori favorentiformazione di trombi

Stabilizzazione della placca

Page 17: ATEROSCLEROSI Atherosclerosis is an inflammatory disease characterized by intense immunological activity, which increasingly threatens human health worldwide