Effects of high glucose and ketosis (acetoacetate, ss-hydroxybutyrate) on PAI-1 secretion in human umbilical vascular endothelial cells.

Plasminogen activator inhibitor 1 (PAI-1) is a known contributor of thrombus formation and cardiovascular diseases. Type 1 diabetes is associated with elevated levels of blood PAI-1 and cardiovascular disease (CVD) incidence. However, type 1 diabetic patients have elevated blood levels of ketone bodies acetoacetate (AA) and 3-β-hydroxybutyrate (BHB). This study examined the hypothesis that hyperketonemia (ketosis) contributes to increased secretion of PAI-1 from the cells that form the vascular endothelium. Human umbilical vein endothelial cells (HUVEC) were treated with different concentrations of AA or BHB in the presence or absence of high glucose (HG) and the amount of PAI-1 protein secreted by these cells into conditioned media was determined. Levels of PAI-1 secreted into conditioned media by these treated cells did not change significantly when compared to controls. High glucose induced a significant increase in PAI-1 secretion, but combination with AA or BHB did not cause significant effects on PAI-1 secretion caused by HG. These results indicate that hyperglycemia but not hyperketonemia is a significant contributor to increased blood levels of PAI-1 associated with type 1 diabetes.