Glucose and insulin independently reduce the fibrinolytic potential of human vascular smooth muscle cells in culture
Abstract
Hyperglycaemia and hyperinsulinaemia have both been related to accelerated atherosclerosis in non-insulin-dependent diabetes mellitus (NIDDM). Plasma fibrinolytic potential is reduced in NIDDM and it is known that glucose and insulin can modulate plasminogen activator inhibitor (PAI-1) and tissue-plasminogen activator (t-PA) secretion and can therefore regulate local fibrinolysis. Vascular smooth muscle cells (vSMC) play an important role in the development of atherosclerotic lesions; however, the role of insulin and glucose in regulating PAI-1 and t-PA production in vSMC is presently not known. Therefore, we cultured arterial vSMC explanted from human umbilical cords and exposed them to increasing concentrations of glucose (5, 12, 20, 27, 35 mmol/l) or insulin (0.1, 0.5, 1, 10 nmol/l) in a serum free medium. After 24 h, PAI-1 and t-PA antigens and activity were evaluated in the culture medium; in cells exposed to 20 mmol/l glucose and to 0.5 nmol/l insulin PAI-1 gene expression was also evaluated. An increase in PAI-1 antigen was observed at each glucose concentration (by 138, 169, 251 and 357% as compared to 5 mmol/l glucose) which was paralleled by an increase in PAI-1 activity. t-PA concentration was also increased by gluco...Continue Reading
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