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 μM) induced migration of human vascular smooth muscle cells (SMC). This was inhibited by antibodies to intercellular adhesion molecule-1 (ICAM-1, 10 μg/ml), and by inhibitors of PI3-kinase (LY294002, 10 μM) and MAPK (mitogen-activated protein kinase) p38 (SB203580, 10 μM). The MEK (MAP kinase kinase) inhibitor PD98059 (10 μM) and the GPIIb/IIIa antagonist abciximab (10 μg/ml) had no effect. ICAM-1 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.