Do platelets protect the heart against ischemia/reperfusion injury or exacerbate cardiac ischemia/reperfusion injury? The role of PDGF, VEGF, and PAF

Acute myocardial infarction (AMI) is one of the main causes of death. It is quite obvious that there is an urgent need to develop new approaches for treatment of AMI. This review analyzes data on the role of platelets in the regulation of cardiac tolerance to ischemia/reperfusion (I/R). It was performed a search of topical articles using PubMed databases. Platelets activated by a cholesterol-enriched diet, thrombin, and myocardial ischemia exacerbate I/R injury of the heart. The P2Y12 receptor antagonists, remote ischemic postconditioning and conditioning alter the properties of platelets. Platelets acquire the ability to increase cardiac tolerance to I/R. Platelet-derived growth factors (PDGFs) increase tolerance of cardiomyocytes and endothelial cells to I/R. PDGF receptors (PDGFRs) were found in cardiomyocytes and endothelial cells. PDGFs decrease infarct size and partially abrogate adverse postinfarction remodeling. Protein kinase C, phosphoinositide 3-kinase, and Akt involved in the cytoprotective effect of PDGFs. Vascular endothelial growth factor increased cardiac tolerance to I/R and alleviated adverse postinfarction remodeling. The platelet-activating factor (PAF) receptor inhibitors increase cardiac tolerance to I/R in vivo. PAF enhances cardiac tolerance to I/R in vitro. It is possible that PAF receptor inhibitors could protect the heart by blocking PAF receptor localized outside the heart. PAF protects the heart through activation of PAF receptor localized in cardiomyocytes or endothelial cells. Reactive oxygen species and kinases are involved in the cardioprotective effect of PAF. Platelets play an important role in the regulation of cardiac tolerance to I/R.