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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

1
Department of Surgery, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
2
Department of Surgery, Medical Center Alkmaar, 1815 JD Alkmaar, The Netherlands
3
Laboratory of Nutrition Biology EA 4466, Faculty of Pharmacy, Paris Descartes University, 75006 Paris, France
4
Clinical Chemistry Department, Hopital Cochin et Hôtel-Dieu, AP-HP, 75014/75004 Paris, France
5
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)
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Abstract

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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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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