Cholesterol feeding accentuates the cyclosporine-induced elevation of renal plasminogen activator inhibitor type 1

Kidney International
C DuymelinckG A Verpooten

Abstract

Long-term cyclosporine (CsA) therapy is accompanied by the occurrence of hypercholesterolemia and renal interstitial fibrosis. The present study investigates the effect of dietary cholesterol on CsA-induced lipid disturbances in the rat and on CsA nephrotoxicity. Since plasminogen activator inhibitor type 1 (PAI-1) is a major inhibitor of matrix degradation and elevated plasma PAI-1 levels are reported to be associated with increased low-density lipoprotein (LDL) cholesterol, PAI-1 was examined in the kidneys of rats fed a sodium-deficient diet, with or without cholesterol. After nine weeks, both diet groups were subdivided into a CsA-treated group and a vehicle-treated group. Although cholesterol feeding significantly aggravated CsA-induced renal function impairment, CsA-induced histological lesions were comparable in both diet groups. Cholesterol feeding significantly decreased high-density lipoprotein (HDL) cholesterol irrespective of the treatment, while CsA treatment significantly elevated serum triglycerides irrespective of the diet. Cholesterol feeding alone did not increase the number of infiltrating cells in the renal interstitium. In contrast, in both diet groups CsA treatment caused a significant influx of macrophage...Continue Reading

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Citations

Oct 24, 2000·Kidney International·J P RerolleE P Rondeau
Apr 1, 2003·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Aiko P J de VriesReinold O b Gans
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Jun 10, 2011·American Journal of Physiology. Renal Physiology·Kristien J LedeganckBenedicte Y De Winter
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Sep 12, 2002·Seminars in Nephrology·Nancy J BrownAgnes B Fogo
Dec 25, 2003·Thrombosis Research·Hiromi HagiwaraToyohiko Ariga

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