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약학대학
약학과
Journal papers
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The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases
Title
The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases
Authors
Ha H.
;
Oh E.Y.
;
Lee H.B.
Ewha Authors
하헌주
SCOPUS Author ID
하헌주
Issue Date
2009
Journal Title
Nature Reviews Nephrology
ISSN
1759-5061
Citation
Nature Reviews Nephrology vol. 5, no. 4, pp. 203 - 211
Indexed
SCI; SCIE; SCOPUS
Document Type
Review
Abstract
The 50 kDa glycoprotein plasminogen activator inhibitor 1 (PAI-1) is the major physiological inhibitor of tissue-type and urokinase-type plasminogen activator. These two molecules convert inactive plasminogen into its fibrin-degrading form, plasmin. Plasma and tissue concentrations of PAI-1 are extremely low under normal circumstances but increase under pathologic conditions. This increase is mediated by many factors, including reactive oxygen species. Increased PAI-1 activity is associated with an increased risk of ischemic cardiovascular events and tissue fibrosis. Whereas the antifibrinolytic property of PAI-1 derives mainly from its inhibition of serine proteases, its profibrotic actions seem to derive from a capacity to stimulate interstitial macrophage recruitment and increase transcription of profibrotic genes, as well as from inhibition of serine proteases. Despite studies in mice that lack or overexpress PAI-1, the biological effects of this molecule in humans remain incompletely understood because of the complexity of the PAI-1-plasminogen- activator-plasmin system. The cardioprotective and renoprotective properties of some currently available drugs might be attributable in part to inhibition of PAI-1. The development of an orally active, high-affinity PAI-1 inhibitor will provide a potentially important pharmacological tool for further investigation of the role of PAI-1 and might offer a novel therapeutic strategy in renal and cardiovascular diseases. © 2009 Macmillan Publishers Limited. All rights reserved.
DOI
10.1038/nrneph.2009.15
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