Induction of plasminogen activator inhibitor by products released from platelets.
Activation of platelets and augmentation of plasma plasminogen activator inhibitor (PAI) type I activity accompany acute myocardial infarction. To determine whether the two may be related, platelet compounds including epidermal growth factor and transforming growth factor beta as well as platelet lysates were studied in rabbits in vivo. After intravenous infusion of epidermal growth factor (1 and 5 micrograms/kg), plasma PAI activity increased sevenfold and 20-fold, peaking at 2 hours. After infusions of transforming growth factor beta (0.2 and 0.5 microgram/kg), plasma PAI activity increased sevenfold and 12-fold but peaked more slowly (at 5 hours). After infusion of platelet lysates (lysates from 2.8 and 5.6 X 10(8) platelets/kg), the increase was 19-fold and 35-fold, with a peak at 4 hours. Platelet lysates induced a pronounced increase of plasma PAI type 1 messenger RNA (Northern blots) in aorta, liver, and myocardium. Anti-transforming growth factor beta neutralizing antibody markedly attenuated the plasma PAI increase. Concentrations in plasma of fibrinogen and alpha 2-antiplasmin were virtually unaffected under all conditions. Thus, platelet-associated growth factors and platelet lysates, shown previously to increase plasma PAI type 1 messenger RNA expression and protein production in cultured hepatocytes and vascular endothelial cells in vitro, augment plasma PAI in vivo as well. Accordingly, activation of platelets and release of platelet-associated growth factors appear to contribute to the increased plasma PAI seen after myocardial infarction.
Cardiovascular Division, Washington University School of Medicine, St. Louis, Missouri 63110.
S
S
Fujii
B E
BE
Sobel
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D006133:Growth Substances / Q000493:pharmacokinetics / Q000494:pharmacology; D007275:Injections, Intravenous; D015849:Plasminogen Inactivators / Q000097:blood* / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D014018:Tissue Distribution
D006133:Growth Substances; D015849:Plasminogen Inactivators; D012333:RNA, Messenger