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Int. J. Mol. Sci. 2015, 16(6), 12230-12242; doi:10.3390/ijms160612230

The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Department of Surgery, Medical Center Alkmaar, 1815 JD Alkmaar, The Netherlands
Laboratory of Nutrition Biology EA 4466, Faculty of Pharmacy, Paris Descartes University, 75006 Paris, France
Clinical Chemistry Department, Hopital Cochin et Hôtel-Dieu, AP-HP, 75014/75004 Paris, France
Clinical chemistry Laboratory, Armand Trousseau hospital, AP-HP, 75012 Paris, France
Author to whom correspondence should be addressed.
Academic Editor: Michael Henein
Received: 8 April 2015 / Revised: 17 May 2015 / Accepted: 26 May 2015 / Published: 29 May 2015
(This article belongs to the Special Issue Atherosclerosis and Vascular Imaging)
View Full-Text   |   Download PDF [1053 KB, uploaded 29 May 2015]   |  


Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques. View Full-Text
Keywords: atherosclerosis; arginine; ADMA; ratio; statins; nitric oxide; cholesterol atherosclerosis; arginine; ADMA; ratio; statins; nitric oxide; cholesterol

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Brinkmann, S.J.H.; Wörner, E.A.; Buijs, N.; Richir, M.; Cynober, L.; van Leeuwen, P.A.M.; Couderc, R. The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine. Int. J. Mol. Sci. 2015, 16, 12230-12242.

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