ICAM-1 and p38 MAPK mediate fibrinogen-induced migration of human vascular smooth muscle cells

Fibrinogen deposition in the vessel wall represents an independent atherogenic risk factor. In Boyden-chamber assays, fibrinogen concentration-dependently (1-100 mu M) induced migration of human vascular smooth muscle cells (SMC). This was inhibited by antibodies to intercellular adhesion molecule-1 (ICAM-1, 10 mu g/ml), and by inhibitors of P13-kinase (LY294002, 10 mu M) and MAPK (mitogen-activated protein kinase) p38 (SB203580, 10 mu M). The MEK (MAP kinase kinase) inhibitor PD98059 (10 mu M) and the GPIIb/IIIa antagonist abciximab (10 mu g/ml) had no effect. ICAM-I antibodies inhibited fibrinogen-induced Akt and p38 phosphorylation. Thus fibrinogen stimulates human SMC migration through binding to ICAM-1 and activation of Akt and p38. (c) 2007 Elsevier B.V. All rights reserved.