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 (PAI-1) in blood and attenuated fibrinolytic activity, hypertriglyceridaemia, and insulin resistance are common in subjects with obesity and non-insulin-dependent diabetes mellitus who are at markedly increased risk for coronary artery disease. To clarify potentially causal relationships between these phenomena, we studied JCR:LA-cp rats, animals that are insulin resistant and prone to vasculopathy. Blood and aortas were obtained from lean and corpulent animals at 1, 2, 4, 6, and 9 months of age. The homozygous corpulent rats were hyperinsulinaemic and hypertriglyceridaemic at all ages tested. Increased activity of PAI-1 was present in blood from corpulent animals at 1, 6, and 9 months of age. Positive correlations were observed between blood PAI-1 and both insulin 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 inhibition of the fibrinolytic system capacity precede gross atherosclerosis.
Schneider
D J
DJ
Department of Medicine, University of Vermont, College of Medicine, Burlington 05405, USA.
Absher
P M
PM
Neimane
D
D
Russell
J C
JC
Sobel
B E
BE
D000375:Aging / Q000097:blood; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000097:blood* / Q000209:etiology / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis; D007328:Insulin / Q000097:blood*; D008297:Male; D009765:Obesity / Q000097:blood / Q000150:complications / Q000378:metabolism; D009924:Organ Culture Techniques; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000097:blood; D051381:Rats; D011922:Rats, Mutant Strains; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood*
D001786:Blood Glucose; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides