NDT Advance Access originally published online on November 20, 2007
Nephrology Dialysis Transplantation 2008 23(2):433-438; doi:10.1093/ndt/gfm718
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© The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Statins and small GTPases: Koch's postulates and chronic kidney disease
Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands
Correspondence and offprint requests to: Jaap A. Joles, Department of Nephrology and Hypertension, F03.226, University of Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands. Tel: +31-30-253-5269; Fax: +31-30-254-3492; E-mail: j.a.joles@umcutrecht.nl
Keywords: choronic kidney disease; HMG-CoA reductase; pleiotropic; statin
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| Introduction |
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Statins (3-hydroxy-3-methylglutaryl-CoA reductase inhibitors) are attracting more and more attention as cardiovascular and renal protective agents. Evidence from in vitro and rodent experiments indicates that this is not mediated via cholesterol-lowering effects, simply because culture dishes and rodents do not respond to statins with a decrease in plasma cholesterol. However, these so-called pleiotropic effects of statins are much harder to prove in humans, where in secondary prevention trials even normo-cholesterolemic subjects exhibit a decrease in LDL cholesterol [1]. Pleiotropic effects of statins appear to depend partly, but not wholly, on the activation of small guanosine triphosphate (GTP)-binding proteins such as Ras, Rho and Rac. The activation depends on a post-translational modification termed isoprenylation. Isoprenoid intermediates of the cholesterol biosynthetic pathway, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) must be attached to these small GTP-binding proteins to achieve activation (Figure 1) [2]. Small GTP-binding proteins
| Koch's postulates |
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| Pleiotropic effects of statins in humans |
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| Differences between statins |
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| Conclusion |
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