On how insulin may influence ageing and become atherogenic throughout the insulin-like growth factor-1 receptor pathway: in vitro studies with human vascular smooth muscle cells.

Background: It is known that growth factors play a role in ageing and atherogenesis, and insulin develops mitogenic activity in vitro.

Objectives: This study focuses on the pathway by which insulin induces proliferation and mobility in vascular smooth muscle cells (SMCs) compared with that of insulin-like growth factor-1 (IGF-1), because they are two basic phenomena for atherogenesis that could also help to understand the role of insulin in the ageing process.

Methods: Bromodeoxyuridine DNA incorporation, chemotaxis and the appearance of membrane ruffles were measured in cultured SMCs after incubation with insulin or IGF-1 in the presence of insulin or IGF-1 receptor-blocking antibodies.

Age-dependent decline of in vitro migration (basal and stimulated by IGF-1 or insulin) of human vascular smooth muscle cells.

Since biological aging causes a decrease in functions such as cell proliferation, we have studied the possible effect of age on the migration capacity of human vascular smooth muscle cells (SMCs). To this aim, the migration activity of cultured SMCs from arteries of male human donors ranging in age from 43-77 years was determined in a Boyden chamber, under basal conditions and after insulin-like growth factor-1 (IGF-1) or insulin stimulation. Migration activity decreased with donor age (r2 = 87%, 85%, and 78%, respectively).