Role of platelet-activating factor in cardiovascular pathophysiology

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglyceri des. PAF acts via a specific receptor that is coupled with a G protein, whi ch activates a phosphatidylinositol-specific phospholipase C. In. this revi ew we focus on the aspects that are more relevant for the cell biology of t he cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell- to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angioge nesis and may affect cardiac function because it exhibits mechanical and el ectrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circ ulation. In pathological conditions, PAF has been involved in the hypotensi on and cardiac dysfunctions occurring in various cardiovascular stress situ ations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic s hock syndromes. In addition, experimental studies indicate that PAF has a c ritical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration o f leukocytes. The finding that human heart can produce PAF, expresses PAF r eceptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysio logy.