Summary
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. [Diabetologia (1998) 41: 141–147]
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Received: 8 July 1997 and in revised form: 23 September 1997
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Schneider, D., Absher, P., Neimane, D. et al. Fibrinolysis and atherogenesis in the JCR:LA-cp rat in relation to insulin and triglyceride concentrations in blood. Diabetologia 41, 141–147 (1998). https://doi.org/10.1007/s001250050882
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DOI: https://doi.org/10.1007/s001250050882