Expression of plasminogen activator inhibitor type I in genotyped human endothelial cell cultures: Genotype-specific regulation by insulin

Patients with non-insulin-dependent diabetes mellitus frequently have been associated with elevation in plasma levels of PAI-1. Part of the variations in individual plasma PAI-1 levels have been attributed to variations in th e PAI-1 gene. In order to determine whether insulin regulates PAI-1 express ion in a genotype-specific manner, individual human umbilical vein ECs (HUV ECs) were genotyped using a HindIII RFLP and incubated in the absence/prese nce of insulin. Treatment of 1/1 PAI-1 genotype HUVECs with insulin increas ed secretion of PAI-1 antigen similar to 1.7 to 2.2-fold and mRNA levels we re increased similar to 1.8 to 2.8-fold, Treatment of HUVECs with actinomyc in D or puromycin completely abolished the induction of PAI-1 by insulin. T he nuclear run-on assays indicated similar to 3-4 fold increase in PAI-1 tr anscription rates. These in vitro studies with the 1/1 PAI-1 genotyped cult ured HUVECs, suggests that hyperinsulinemia may be expected to increase EC PAI-1 synthesis in those patients with the responsive 1/1 genotype.