PHENOTYPIC CHANGES IN VASCULAR SMOOTH-MUSCLE CELLS DURING AGING - INSULIN EFFECT ON MIGRATION

We examined the mechanisms by which insulin may be atherogenic during aging. We postulated that an increase in insulin secretion during agin g produces growth factor effects on vascular smooth muscle cells (VSMC s), promoting these cells to synthesize collagen and to migrate. We ha ve previously demonstrated that insulin stimulates collagen synthesis and release in senescent VSMCs that were obtained from a human organis m with high levels of insulin secretion. Using the same experimental m odel, we now study the effects of insulin on VSMC migration. We demons trate that insulin has a chemoattractant effect on VSMCs which occurs through insulin binding to its own specific receptors as opposed to it s effect on collagen production. Blocking the insulin receptor signifi cantly eliminates the insulin effect on cell migration. At the same mo larity, the chemotactic effect of insulin is less pronounced than that of insulin-like growth factor-1. In spite of different mechanisms, th ere is a remarkable correlation between the insulin effects on collage n secretion and cell migration (r(2): = 97%, p < 0.0005). Our results indicate that distinct but closely related mechanisms may exist by whi ch insulin becomes atherogenic. Our results also suggest the importanc e of normal aging processes in the development of atherosclerosis.