Insulin-Like Growth Factor and Platelet Activation the Role in Arterial Injury and Restenosis

Abstract 5267

Insulin-like growth factor (IGF-1) is an activator of the PI3K/AKT (serine/threonine protein kinase) signalling pathway. It can also stimulate cell growth (PDGF, PDAF, VEGF, TGF-alfa and beta), and cellular proliferation, and is a powerful stimulator of directed migration of VSMC (vascular smooth muscle cells). The deregulated action of IGF-1 influences coronary artery disease (CAD) by promoting neo-intimal hyperplasia and leukocyte recruitment, pro-mytotic activity (MAPK: mitogen-activated protein kinases, serine/threonine kinase), and extracellular matrix synthesis in atherosclerotic lesions; it also increases platelet activity, and the expression of P-selectin, IL-6 and platelet CD62. This growth factors may also promote chemotaxis, LDL-cholesterol uptake, and the release of pro-inflammatory cytokines, finally it is a strong inhibitor of apoptosis (BAX, Fas/FasL); in other words, a high level of IGF-1 is a strong risk marker for ischemic heart disease.

We have studied a group of 140 patients (92 males and 48 females, mean age was 58 years, range 46–68 years); 72 patients with CAD in early stage of restenosis and 68 control. Patients with arterial restenosis have significantly high levels of IGF-1 (142.8 ng/ml +/− 24.2 ng/ml) that appear closely related to recurrence, than control subjects (mean level of IGF-1: 98.6 ng/ml +/− 14.4 ng/ml).

Additional investigations are needed to determine the exact weight of IGF-1 from a slightly clinical point of view, as this marker showed interestingly to have a key role in the pathogenesis of atherosclerosis.