Abstract
Thrombotic complications of vascular disease constitute the leading cause of morbidity and mortality in much of the developed world. Current drug therapies available to treat the thrombotic component of arterial and venous vascular complications remain limited. Novel safe and effective treatment strategies to reduce formation of occlusive thrombosis will likely have a major impact on reducing the economic burden of vascular disease on the healthcare system. Enhancing endogenous fibrinolysis by targeting plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of circulating plasminogen activators, has been shown to be effective in markedly attenuating the formation of arterial and venous occlusive thrombosis in animal models. In addition, animal and human studies of PAI-1 deficiency indicate that spontaneous bleeding complications associated with even complete PAI-1 deficiency would be rare. Patients most likely to benefit from PAI-1 inhibition would be those at high risk for vascular events where PAI-1 is elevated, such as is observed in obesity, diabetes and the metabolic syndrome. Since obesity and metabolic syndrome are now epidemic, and will likely have a major adverse impact on vascular thrombotic events, it may be time to test the clinical effectiveness of PAI-1 inhibition in a patient population at high risk for vascular thrombosis.
Keywords: urokinase-type plasminogen activator, atherothrombosis, protease activity, thrombolysis, vitronectin deficient mice
Current Drug Targets
Title: Plasminogen Activator Inhibitor-1 in Vascular Thrombosis
Volume: 8 Issue: 9
Author(s): Randal J. Westrick and Daniel T. Eitzman
Affiliation:
Keywords: urokinase-type plasminogen activator, atherothrombosis, protease activity, thrombolysis, vitronectin deficient mice
Abstract: Thrombotic complications of vascular disease constitute the leading cause of morbidity and mortality in much of the developed world. Current drug therapies available to treat the thrombotic component of arterial and venous vascular complications remain limited. Novel safe and effective treatment strategies to reduce formation of occlusive thrombosis will likely have a major impact on reducing the economic burden of vascular disease on the healthcare system. Enhancing endogenous fibrinolysis by targeting plasminogen activator inhibitor-1 (PAI-1), the primary inhibitor of circulating plasminogen activators, has been shown to be effective in markedly attenuating the formation of arterial and venous occlusive thrombosis in animal models. In addition, animal and human studies of PAI-1 deficiency indicate that spontaneous bleeding complications associated with even complete PAI-1 deficiency would be rare. Patients most likely to benefit from PAI-1 inhibition would be those at high risk for vascular events where PAI-1 is elevated, such as is observed in obesity, diabetes and the metabolic syndrome. Since obesity and metabolic syndrome are now epidemic, and will likely have a major adverse impact on vascular thrombotic events, it may be time to test the clinical effectiveness of PAI-1 inhibition in a patient population at high risk for vascular thrombosis.
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Cite this article as:
Westrick J. Randal and Eitzman T. Daniel, Plasminogen Activator Inhibitor-1 in Vascular Thrombosis, Current Drug Targets 2007; 8 (9) . https://dx.doi.org/10.2174/138945007781662328
DOI https://dx.doi.org/10.2174/138945007781662328 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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