Novel role of platelets in mediating inflammatory responses and ventricular rupture or remodeling following myocardial infarction.
OBJECTIVE
The goal of this study was to investigate the role of platelets in systemic and cardiac inflammatory responses and the development of postinfarct ventricular complications, as well as the efficacy of antiplatelet interventions.


RESULTS
Using a mouse myocardial infarction (MI) model, we determined platelet accumulation and severity of inflammation within the infarcted myocardium by immunohistochemistry and biochemical assays, analyzed peripheral blood platelet-leukocyte conjugation using flow cytometry, and tested antiplatelet interventions, including thienopyridines and platelet depletion. Platelets accumulated within the infarcted region early post-MI and colocalized with inflammatory cells. MI evoked early increase in circulating platelet-leukocyte conjugation mediated by P-selectin/P-selectin glycoprotein ligand-1. Antiplatelet interventions inhibited platelet-leukocyte conjugation in peripheral blood, inflammatory infiltration, content of matrix metalloproteinases or plasminogen activation, and expression of inflammatory mediators in the infarcted myocardium (all P<0.05) and lowered rupture incidence (P<0.01). Clopidogrel therapy alleviated the extent of chronic ventricular dilatation by serial echocardiography.


CONCLUSIONS
Platelets play a pivotal role in promoting systemic and cardiac inflammatory responses post-MI. Platelets accumulate within the infarcted myocardium, contributing to regional inflammation, ventricular remodeling, and rupture. Antiplatelet therapy reduces the severity of inflammation and risk of post-MI complications, demonstrating a previously unrecognized protective action.
Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Yang
Y
Liu
Xiao-Ming
XM
Gao
Lu
L
Fang
Nicole L
NL
Jennings
Yidan
Y
Su
Xu
X
Q
Andre L
AL
Samson
Helen
H
Kiriazis
Xin-Feng
XF
Wang
Leonard
L
Shan
Sharelle A
SA
Sturgeon
Robert L
RL
Medcalf
Shaun P
SP
Jackson
Anthony M
AM
Dart
Xiao-Jun
XJ
Du
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006342:Heart Rupture, Post-Infarction / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D007150:Immunohistochemistry; D007249:Inflammation / Q000097:blood / Q000209:etiology* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000097:blood*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019007:P-Selectin / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D017395:Plasminogen Activator Inhibitor 1; D010975:Platelet Aggregation Inhibitors; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator