Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:61-69
© 2000 American Heart Association, Inc.
Vascular Biology |
Improvement of Nitric Oxide–Dependent Vasodilatation by HMG-CoA Reductase Inhibitors Through Attenuation of Endothelial Superoxide Anion Formation
From the Department of Cardiovascular Physiology, University of Göttingen (A.H.W., T.K., M.H.); the Institute of Pathophysiology, University of Halle (U.R.); and the Institute of Pharmacology and Toxicology, University of Freiburg (I.J.), Germany.
Correspondence to Dr Markus Hecker, Abteilung Herz- und Kreislaufphysiologie, Georg-August-Universität Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany.
Abstract—Three
3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase
inhibitors (HCRIs), atorvastatin, pravastatin,
and cerivastatin, inhibited phorbol ester–stimulated superoxide anion
(O2-) formation in
endothelium-intact segments of the rat aorta in a time-
and concentration-dependent manner (maximum inhibition of 70% after 18
hours at 1 to 10 µmol/L). The HMG-CoA reductase product
mevalonic acid (400 µmol/L) reversed the inhibitory
effect of the HCRIs, which, conversely, was mimicked by inactivation of
p21 Rac with Clostridium sordellii lethal toxin but not
by inactivation of p21 Rho with Clostridium
botulinum exoenzyme (C3). A mevalonate-sensitive inhibition of
phorbol ester–stimulated O2- formation by
atorvastatin was also observed in porcine cultured
endothelial cells and in a murine macrophage
cell line. In the rat aorta, no effect of the HCRIs on protein kinase
C, NADPH oxidase, or superoxide dismutase (SOD) activity and expression
was detected, whereas that of endothelial nitric oxide
(NO) synthase was enhanced 
2-fold. Moreover, exposure of the
segments to atorvastatin resulted in a significant improvement of
endothelium-dependent NO-mediated relaxation, and this
effect was abolished in the presence of SOD. Taken together, these
findings suggest that in addition to augmenting
endothelial NO synthesis, HCRIs inhibit
endothelial O2- formation by
preventing the isoprenylation of p21 Rac, which is critical for the
assembly of NADPH oxidase after activation of protein kinase C. The
resulting shift in the balance between NO and
O2- in the endothelium
improves endothelial function even in healthy blood
vessels and therefore may provide a reasonable explanation for the
beneficial effects of HCRIs in patients with coronary heart
disease in addition to or as an alternative to the reduction in serum
LDL cholesterol.
Key Words: HMG-CoA reductase inhibitor(s) • endothelial dysfunction • coronary heart disease • nitric oxide • superoxide anion • NADPH oxidase • p21 Rac
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|
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|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
H. Azumi, N. Inoue, Y. Ohashi, M. Terashima, T. Mori, H. Fujita, K. Awano, K. Kobayashi, K. Maeda, K. Hata, et al. Superoxide Generation in Directional Coronary Atherectomy Specimens of Patients With Angina Pectoris: Important Role of NAD(P)H Oxidase Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1838 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Sposito and M. J. Chapman Statin Therapy in Acute Coronary Syndromes: Mechanistic Insight Into Clinical Benefit Arterioscler Thromb Vasc Biol, October 1, 2002; 22(10): 1524 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Bates, C. E. Ruggeroli, S. Goldman, and M. A. Gaballa Simvastatin restores endothelial NO-mediated vasorelaxation in large arteries after myocardial infarction Am J Physiol Heart Circ Physiol, August 1, 2002; 283(2): H768 - H775. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Delbosc, J.-P. Cristol, B. Descomps, A. Mimran, and B. Jover Simvastatin Prevents Angiotensin II-Induced Cardiac Alteration and Oxidative Stress Hypertension, August 1, 2002; 40(2): 142 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Vecchione and R. P. Brandes Withdrawal of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Elicits Oxidative Stress and Induces Endothelial Dysfunction in Mice Circ. Res., July 26, 2002; 91(2): 173 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sardo, M. Castaldo, M. Cinquegrani, M. Bonaiuto, A. Maesano, A. Versace, M. Spadaro, S. Campo, G. Nicocia, D. Altavilla, et al. Effects of Atorvastatin Treatment on sICAM-1 and Plasma Nitric Oxide Levels in Hypercholesterolemic Subjects Clinical and Applied Thrombosis/Hemostasis, July 1, 2002; 8(3): 257 - 263. [Abstract] [PDF]
|
|
|
|
|
|
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|
|
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 S. I. McFarlane, R. Muniyappa, R. Francisco, and J. R. Sowers Pleiotropic Effects of Statins: Lipid Reduction and Beyond J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1451 - 1458. [Abstract] [Full Text] [PDF]
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
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U. Laufs, M. Endres, F. Custodis, K. Gertz, G. Nickenig, J. K. Liao, and M. Bohm Suppression of Endothelial Nitric Oxide Production After Withdrawal of Statin Treatment Is Mediated by Negative Feedback Regulation of Rho GTPase Gene Transcription Circulation, December 19, 2000; 102(25): 3104 - 3110. [Abstract] [Full Text] [PDF]
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V. J. Thannickal and B. L. Fanburg Reactive oxygen species in cell signaling Am J Physiol Lung Cell Mol Physiol, December 1, 2000; 279(6): L1005 - L1028. [Abstract] [Full Text] [PDF]
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U. Laufs and J. K. Liao Targeting Rho in Cardiovascular Disease Circ. Res., September 29, 2000; 87(7): 526 - 528. [Full Text] [PDF]
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M. S. Wolin How Could a Genetic Variant of the p22phox Component of NAD(P)H Oxidases Contribute to the Progression of Coronary Atherosclerosis? Circ. Res., March 3, 2000; 86(4): 365 - 366. [Full Text] [PDF]
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W. Ni, K. Egashira, C. Kataoka, S. Kitamoto, M. Koyanagi, S. Inoue, and A. Takeshita Antiinflammatory and Antiarteriosclerotic Actions of HMG-CoA Reductase Inhibitors in a Rat Model of Chronic Inhibition of Nitric Oxide Synthesis Circ. Res., August 31, 2001; 89(5): 415 - 421. [Abstract] [Full Text] [PDF]
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S. Nasreen, T. Nabika, H. Shibata, H. Moriyama, K. Yamashita, J. Masuda, and S. Kobayashi T-786C Polymorphism in Endothelial NO Synthase Gene Affects Cerebral Circulation in Smokers: Possible Gene-Environmental Interaction Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 605 - 610. [Abstract] [Full Text] [PDF]
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