Interaction between insulin-like growth factor-1 and atherosclerosis and vascular aging.

Abstract

The process of vascular aging encompasses alterations in the function of endothelial (ECs) and vascular smooth muscle cells (VSMCs) via oxidation, inflammation, cell senescence and epigenetic modifications, increasing the probability of atherosclerosis. Aged vessels exhibit decreased endothelial antithrombogenic properties, increased reactive oxygen species generation, inflammatory signaling and migration of VSMCs to the subintimal space, impaired angiogenesis and increased elastin degradation. The key initiating step in atherogenesis is subendothelial accumulation of apolipoprotein B-containing low-density lipoproteins resulting in activation of ECs and recruitment of monocytes. Activated ECs secrete 'chemokines' that interact with cognate chemokine receptors on monocytes and promote directional migration. Recruitment of immune cells establishes a proinflammatory status, further causing elevated oxidative stress, which in turn triggers a series of events including apoptotic or necrotic death of vascular and nonvascular cells. Increased oxidative stress is also considered to be a key factor in mechanisms of aging-associated changes in tissue integrity and function. Experimental evidence indicates that insulin-like growth factor-1 exerts antioxidant, anti-inflammatory and pro-survival effects on the vasculature, reducing atherosclerotic plaque burden and promoting features of atherosclerotic plaque stability.