Platelet activating factor: the good and the bad in the ischemic/reperfused heart

Abstract

The present review is focused on the dual role played by platelet-activating factor (PAF) in ischemia and reperfusion (I/R) injury of the heart. Although the involvement of PAF in the pathogenesis of myocardial reperfusion injury is well established, in the last few years it has emerged that very low concentrations of PAF exert cardioprotective effects, comparable to that afforded by ischemic preconditioning (IP). PAF is a potent phosphoglyceride involved in different pathophysiological conditions affecting the cardiovascular system, including the development of myocardial I/R injury. PAF is released from the I/R myocardium in concentrations (1-10 nmol/L) high enough to negatively modulate coronary circulation as well as electrical and contractile activities. PAF may act either directly, via generation of secondary mediators, or through the activation of inflammatory cells like platelets and polymorphonuclear neutrophils, which exacerbate postischemic myocardial injury. The effects of PAF are mediated through specific receptors (PAFRs) that belong to the superfamily of G protein-coupled receptors. Since cardiomyocytes not only produce PAF but also possess PAFRs, it is likely that PAF acts as an autocrine/paracrine mediator. Although the negative effects exerted by high concentrations of PAF are well established, several recent findings from our and other laboratories have demonstrated that very low concentrations (pmol/L) of PAF infused before ischemia induce cardioprotective effects similar to those afforded by IP, and that endogenous PAF production participates in the induction of IP itself. The IP-like action exerted by low concentrations of PAF is due to the activation/phosphorylation of kinases included in the reperfusion injury salvage kinase (RISK) pathway, such as protein kinase C, Akt/PkB and nitric oxide synthase. Together with the activation of mitochondrial K(ATP) channels, these events may allow prevention of mitochondrial permeability transition pores opening at reperfusion. Moreover, the nitric oxide-dependent S-nitrosylation of L-type Ca(2+) channels induced by PAF reduces intracellular Ca(2+) overload.

Elevated Plasma Platelet Activating Factor, Platelet Activating Factor Acetylhydrolase Levels and Risk of Coronary Heart Disease or Blood Stasis Syndrome of Coronary Heart Disease in Chinese: A Case Control Study

“…Platelet activating factor (PAF) is a phospholipid with the chemical structure 1-o-alkyl-2-acetyl-sn-glycero-3-phosphocholine [23,24]. It is now known that PAF is a potent mediator of inflammation and leukocyte activator, which has many biomedical effects including attraction and activation of leukocytes and platelet; increasing vascular permeability; promoting chemotaxis, aggregation, granule secretion and oxygen radical generation of leukocytes; and enhancement of adhesion of leukocytes to endothelium [25,26].…”

Ginkgolide B Reduces the Degradation of Membrane Phospholipids to Prevent Ischemia/Reperfusion Myocardial Injury in Rats

“…PAF plays a critical role in the development of myocardial ischemia-reperfusion injury. It has been reported that PAF decreases myocardial contractility, increases coronary artery resistance and microvascular permeability and induces arrhythmias [4,5,13,14] . PAF is produced and released mainly from injured vascular endothelial cells and neutrophils, but it also can be synthesized and released from ischemic/reperfusion myocardium [4] .…”

Effect of safflower yellow on platelet activating factor mediated platelet activation in patients with coronary heart disease

“…PAF can be synthesized by platelets, white blood cells, endothelial cells and other cells and has wide biological activities. There is evidence showing that PAF is an important mediator in numerous diseases and closely related to ischemia-reperfusion injury, coronary heart disease, atherosclerosis, cerebrovascular diseases and other ischemia related cardiovascular and cerebrovascular diseases (Penna et al, 2011). In these diseases, the platelet aggregation is active and some thrombogenic factors including TXA2, β2TG, 5-HT, etc are released leading to the tendency to thrombosis.…”

“…In the development of these diseases, platelet activation is frequently found accompanied by increase in free calcium in the platelets. Platelet activating factor (PAF) is an inflammatory cytokine synthesized in multiple cells and has been found to be the most potent inducer of platelet aggregation (Penna et al, 2011). Study has confirmed than PAF involves in the occurrence and development of numerous human disease and plays important roles in the pathophysiology of some cardiovascular and cerebrovascular diseases (Shen and Li, 1991).…”