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. 2015 May 29;16(6):12230-42.
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

Saskia J H Brinkmann  1 , Elisabeth A Wörner  2 , Nikki Buijs  3   4 , Milan Richir  5   6 , Luc Cynober  7   8 , Paul A M van Leeuwen  9 , Rémy Couderc  8   10
Affiliations

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

Saskia J H Brinkmann et al. Int J Mol Sci. .

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.

Keywords: ADMA; arginine; atherosclerosis; cholesterol; nitric oxide; ratio; statins.

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Figures

Figure 1
Figure 1
Schematic overview of the interactions between arginine, asymmetric dimethylarginine (ADMA), dimethylarginine dimethylaminohydrolase (DDAH), and nitric oxide synthase (NOS). PRMTs, protein arginine methyltransferases.
Figure 2
Figure 2
Pearson correlation between ∆ADMA (T0–T8, n = 4 per group) and aortic lesions in the distal aorta (r = 0.677, p = 0.01) and total aorta (r = 0.599, p = 0.03).
Figure 3
Figure 3
Pearson correlation between arginine/ADMA ratio and the difference in cholesterol levels over time in the statine (n = 8) and statine-arginine group (n = 8) (S: r = 0.461, SA: r = 0.699).
Figure 4
Figure 4
Pearson correlation between arginine/ADMA ratio T8 and NO levels at T8 in the statine (n = 8) and control group (n = 9) (S: r = 0.709, p = 0.049, C: r = 0.694, p = 0.056).
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