Effects of Insulin on the Vasculature

Danna      M. Breen; Adria      Giacca

Abstract

Revascularization procedures used for the treatment of cardiovascular disease can be associated with restenosis, although drug-coated stents have greatly reduced this complication. Both type 2 diabetes (T2DM) and metabolic syndrome (MetS) are associated with a high risk for atherosclerosis and restenosis. Insulin resistance, defined as the inability of insulin to exert its metabolic actions, characterizes both T2DM and MetS. Recent data suggest that insulin resistance is directly implicated in atherosclerosis/restenosis, because of the unresponsiveness to the vasculoprotective action of insulin, including its phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase mediated enhancement of endothelial function. However, insulin also has ‘atherogenic’ actions, including enhancement of vascular smooth muscle cell (VSMC) proliferation, which are mitogen-activated protein kinase-mediated. These ‘atherogenic’ actions are less affected by insulin resistance, which mainly involves the PI3K pathway. The role of insulin in the atherosclerotic disease process is still highly controversial, where some investigators view insulin as a growth factor with pro-atherogenic effects while some others believe insulin resistance to be pro-atherogenic rather than insulin itself. We attempt to produce a balanced review with a focus on the effect of insulin in vivo, in animal models of atherosclerosis and restenosis.

Keywords: Insulin, restenosis, atherosclerosis, metformin, hypercholesterolemia, hyperinsulinemia, cardiovascular disease, type 2 diabetes mellitus, metabolic syndrome, glucose intolerance, hypertension, thiazolidinediones