FIBRINOLYSIS AND ATHEROGENESIS IN THE JCR-LA-CP RAT IN RELATION TO INSULIN AND TRIGLYCERIDE CONCENTRATIONS IN BLOOD

Increased concentrations of plasminogen activator inhibitor type-1 (PA I-1) in blood and attenuated fibrinolytic activity, hypertriglyceridae mia, and insulin resistance are common in subjects with obesity and no n-insulin-dependent diabetes mellitus who are at markedly increased ri sk for coronary artery disease. To clarify potentially causal relation ships between these phenomena, we studied JCR:LA-cp rats, animals that are insulin resistant and prone to vasculopathy. Blood and aortas wer e obtained from lean and corpulent animals at 1, 2, 4, 6, and 9 months of age. The homozygous corpulent rats were hyperinsulinaemic and hype rtriglyceridaemic at all ages tested. Increased activity of PAI-1 was pre sent in blood from corpulent animals at 1, 6, and 9 months of age. Positive correlations were observed between blood PAI-1 and both insu lin and triglycerides. As judged from results with aortic rings in in vitro culture, the increased PAI-1 in blood was anteceded by increased expression of PAI-1 in arterial walls. Thus, changes indicative of in hibition of the fibrinolytic system capacity precede gross atheroscler osis.