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The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases.
- Source :
-
Nature reviews. Nephrology [Nat Rev Nephrol] 2009 Apr; Vol. 5 (4), pp. 203-11. - Publication Year :
- 2009
-
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.
- Subjects :
- Animals
Cardiovascular Diseases metabolism
Humans
Kidney Diseases metabolism
Mice
Oxidation-Reduction
Polymorphism, Genetic physiology
Renin-Angiotensin System physiology
Cardiovascular Diseases etiology
Cardiovascular Diseases prevention & control
Kidney Diseases etiology
Kidney Diseases prevention & control
Plasminogen Activator Inhibitor 1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1759-507X
- Volume :
- 5
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Nature reviews. Nephrology
- Publication Type :
- Academic Journal
- Accession number :
- 19322185
- Full Text :
- https://doi.org/10.1038/nrneph.2009.15