PAI-1 and TGF-β

Abstract

Atherosclerosis is an extremely complex disease process in which genetic, lipid, cellular, and immunologic factors combine to determine the location, severity, and timing of lesion development and clinical events.1 With the current epidemic of obesity and the metabolic syndrome, additional factors are now recognized as contributors to the vascular disease equation, including plasminogen activator inhibitor-1 (PAI-1),2 which is one of the critical physiological regulators of plasminogen activation. PAI-1 accumulates in atherosclerotic lesions3 and contributes to a variety of vascular pathologies including coronary artery thrombosis4 and perivascular fibrosis.5,6 Numerous factors are known to regulate vascular PAI-1 production, including nitric oxide (NO), which directly suppresses PAI-1 expression.7 Simply inhibiting vascular NO production stimulates arterial PAI-1 accumulation and promotes the development of PAI-1–dependent perivascular fibrosis.8 Other factors promote vascular pathology and arteriosclerosis through mechanisms that likely involve PAI-1, including Angiotensin II9 and …