Platelet-activating factor and cardiac diseases: therapeutic potential for PAF inhibitors.
Platelet-activating factor (PAF) is a potent phospholipid mediator released from inflammatory cells in response to diverse immunologic and non-immunologic stimuli. Animal studies have implicated PAF as a major mediator involved in coronary artery constriction, modulation of myocardial contractility and the generation of arrhythmias which may bear on cardiac disorders such as ischemia, infarction and sudden cardiac death. PAF effects are induced by direct actions of PAF on cardiac tissue to modify chronotropic and inotropic activity, or indirectly via the release of eicosanoids such as thromboxane A2 (TXA2), leukotrienes (LT) or cytokines (TNF alpha). The development of selective, high affinity PAF receptor antagonists has permitted investigations on the role of PAF in experimental animal models of cardiac injury. In vivo and in vitro studies strongly suggest that PAF receptor antagonists might convey therapeutic benefits in ischemic conditions and certain arrhythmias. In addition, PAF antagonists might have a cardiac allograft-preservation effect. Although clinical studies with PAF receptor antagonists in patients with cardiac diseases have not yet been reported, the experimental results to date suggest that PAF receptor antagonists might be useful in some specific cardiac disorders in humans.
Feuerstein
G
G
Department of Cardiovascular, UW2511, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939, USA.
Rabinovici
R
R
Leor
J
J
Winkler
J D
JD
Vonhof
S
S
D000818:Animals; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000188:drug therapy* / Q000378:metabolism; D016027:Heart Transplantation; D006801:Humans; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor