Insulin-like growth factors I and II (
IGF-I and -II) and their regulatory
proteins are secreted by cells of the cardiovascular system. They are growth promoters for arterial cells and mediators of
cardiovascular disease. IGFs are bound to
IGF binding proteins (IGFBPs), which modulate IGF
ligand-receptor interaction and consequently to IGF action. IGFBPs are in turn posttranslationally modulated by specific
proteases. This dynamic balance (IGFs, IGFBPs, and
IGFBP proteases) constitutes the IGF axis and ultimately determines the extent of IGF-dependent cellular effects. Dysregulated actions of this axis influence
coronary atherosclerosis through effects on vascular smooth muscle cell growth, migration, and extracellular matrix synthesis in the
atherosclerotic plaque.
IGF-I promotes macrophage chemotaxis, excess
LDL cholesterol uptake, and release of proinflammatory
cytokines. Endothelial cells also receive the effects of IGFs stimulating their migration and organization forming capillary networks. Neointimal
hyperplasia of restenosis after coronary artery injury is also modulated by the IGF axis. IGFs stimulate vascular smooth muscle cell proliferation and migration to form the
neointima and upregulate
tropoelastin synthesis after disruption of the elastic layer. Understanding IGF axis regulation establishes a scientific basis for strategies directed to limit or reverse plaque growth and vulnerability in
atherosclerosis and in the neointimal
hyperplasia of restenosis.