Regulation of arterial remodeling and angiogenesis by urokinase-type plasminogen activator.
A wide variety of disorders are associated with an imbalance in the plasminogen activator system, including inflammatory diseases, atherosclerosis, intimal hyperplasia, the response mechanism to vascular injury, and restenosis. Urokinase-type plasminogen activator (uPA) is a multifunctional protein that in addition to its fibrinolytic and matrix degradation capabilities also affects growth factor bioavailability, cytokine modulation, receptor shedding, cell migration and proliferation, phenotypic modulation, protein expression, and cascade activation of proteases, inhibitors, receptors, and modulators. uPA is the crucial protein for neointimal growth and vascular remodeling. Moreover, it was recently shown to be implicated in the stimulation of angiogenesis, which makes it a promising multipurpose therapeutic target. This review is focused on the mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury and the means by which it modulates gene expression in vascular cells. The role of domain specificity of urokinase in these processes is also discussed.
Tkachuk
Vsevolod A
VA
Cardiology Research Centre, Laboratory of Molecular Endocrinology, Moscow 121552, Russia.
Plekhanova
Olga S
OS
Parfyonova
Yelena V
YV
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D001158:Arteries / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D003324:Coronary Artery Disease / Q000209:etiology; D023903:Coronary Restenosis / Q000209:etiology; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000502:physiology*; D014657:Vasculitis / Q000209:etiology
D018836:Inflammation Mediators; D014568:Urokinase-Type Plasminogen Activator