Renal glomerular and interstitial fibrosis is widely viewed as the final common pathway to renal failure, regardless of the initiating injury. Similarly, the renin-angiotensin-aldosterone system (RAAS) plays an important role in the progression of renal disease. This review explores the hypothesis that the RAAS causes injury and fibrosis, in part, through effects on plasminogen activator inhibitor-1 (PAI-1), the major physiologic inhibitor of plasminogen activators in vivo. PAI-1, by inhibiting the production of plasmin from plasminogen, tips the balance in favor of extracellular matrix accumulation and promotes fibrosis. Interruption of the RAAS decreases both PAI-1 expression and fibrosis in animal models. These findings have implications for the clinical management of renal disease.
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