Effects of Rosuvastatin on Serum Asymmetric Dimethylarginine Levels and Atrial Structural Remodeling in Atrial Fibrillation Dogs

Li, Jingjie; Feng, Wang; Qu, Xiufen

doi:10.1111/j.1540-8159.2011.03308.x

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…One study found that treatment with statins elevates levels of DDAH, which metabolizes ADMA [ 30 ]. Moreover, statins have shown to be able to decrease plasma levels of ADMA in different types of study settings [ 31 , 32 , 33 , 34 , 35 , 36 ]. Atorvastatin specifically is demonstrated to increase levels of DDAH in rats and humans and thereby to decrease plasma ADMA levels [ 37 , 38 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

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

Brinkmann

Wörner

Buijs

et al. 2015

IJMS

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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.

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Section: Resultsmentioning

confidence: 99%

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

Brinkmann

Wörner

Buijs

et al. 2015

IJMS

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“…In recent years, several animal models of AF [ 11 – 13 , 20 , 21 ] have been developed to investigate the molecular mechanism contributing to atrial remodeling. Among them, the dog [ 11 , 14 , 20 ] and rabbit [ 17 , 19 , 21 ] AF models induced by RAP are widely used. However, if atrioventricular block is not performed, dogs will develop significant LV dysfunction induced by RAP [ 20 ], whereas rabbits will not [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…The pacing time of our rabbit AF model is relatively short compared with the previous canine AF model [ 14 , 20 ], but rabbits have already had obvious atrial enlargement and interstitial fibrosis. In the previous canine AF model, after 4–6 weeks of RAP, LA volumes were nearly 2 times that at baseline [ 14 , 28 ], and atrial fibrosis of the control group was nearly 9–10 times that of the sham group [ 20 , 28 ]. In our model, after 3 weeks of RAP, LA volumes were nearly 4 times that at baseline, and atrial fibrosis of the control group was nearly 7 times that of the sham group.…”

Section: Discussionmentioning

confidence: 99%

“…Recent meta-analyses showed that the use of statins is associated with a decreased risk of AF in patients with sinus rhythm [ 9 , 10 ]. Some studies also reported that statins could attenuate atrial electrical or structural remodeling in dog and goat AF models [ 11 – 14 ]. However, the molecular mechanism by which statins may prevent AF has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing

Yang

Dang

et al. 2016

BMC Cardiovasc Disord

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BackgroundAccumulating evidence suggests that myeloperoxidase (MPO) is involved in atrial remodeling of atrial fibrillation (AF). Statins could reduce the MPO levels in patients with cardiovascular diseases. This study evaluated the effects of atorvastatin on MPO level and atrial remodeling in a rabbit model of pacing-induced AF.MethodsEighteen rabbits were randomly divided into sham, control and atorvastatin groups. Rabbits in the control and atorvastatin groups were subjected to rapid atrial pacing (RAP) at 600 bpm for 3 weeks, and treated with placebo or atorvastatin (2.5 mg/kg/d), respectively. Rabbits in the sham group did not receive RAP. After 3 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, atrial effective refractory period (AERP) and AF inducibility were measured by atrial electrophysiological examination, and histological changes were evaluated by Masson trichrome-staining. The L-type calcium channel α1c (Cav1.2), collagen I and III, MPO, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by real time polymerase chain reaction and/or western blot.ResultsAll rabbits were found to have maintained sinus rhythm after 3 weeks of RAP. Atrial burst stimulation induced sustained AF (>30 min) in 5, 4, and no rabbits in the control, atorvastatin, and sham groups, respectively. The AERP shortened and Cav1.2 mRNA level decreased in the control group, but these changes were suppressed in the atorvastatin group. Obvious left atrial enlargement and dysfunction was found in both control and atorvastatin groups. Compared with the control group, these echocardiograhic indices of left atrium did not differ in the atorvastatin group. Prominent atrial fibrosis and increased levels of collagen I and III were observed in the control group but not in the atorvastatin group. The mRNA and protein levels of MPO, MMP-2 and MMP-9 significantly increased in the control group, but these changes were prevented in the atorvastatin group.ConclusionTreatment with atorvastatin prevented atrial remodeling in a rabbit model of RAP-induced AF. The reduction of levels of atrial MPO, MMP-2 and MMP-9 may contribute to the prevention of atorvastatin on atrial remodeling.

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“…Rosuvastatin significantly decreased ADMA levels in spontaneously hypertensive rats independently of any lowering in cholesterol levels effect [228]. In another experimental study, rosuvastatin decreased to normal values the elevated ADMA levels in dogs with atrial fibrillation [229]. Atorvastatin has also been reported to modulate DDAH/ADMA pathway in insulin-resistant rats by reversing low DDAH levels, low DDAH-1 aortic expression and high ADMA levels, suggesting that DDAH may be another target of statins through which they exert their antiatherogenic actions [196].…”

Section: Statinsmentioning

confidence: 90%

Asymmetric Dimethylarginine: Clinical Significance and Novel Therapeutic Approaches

Tousoulis

Georgakis²,

Oikonomou³

et al. 2015

CMC

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Asymmetric dimethylarginine (ADMA) is a competitive endogenous inhibitor of nitric oxide synthase with a key role in the pathophysiology of endothelial dysfunction, in the progression of atherosclerosis and in cardiovascular diseases. Statins, renin-angiotensin-aldosterone system inhibitors, blood glucose lowering agents, insulin sensitizers, beta-blockers, estrogen replacement therapy, antioxidants, complex B vitamins, L-arginine and acetylsalicylic acid have been evaluated for their ability to reduce ADMA levels or inhibit its actions. Despite the major beneficial effects of these agents in cardiovascular disease, research has shown that their favorable actions are only partially mediated by reducing ADMA levels or by bypassing its effect in nitric oxide synthesis. Novel therapeutic approaches targeting selectively ADMA are encouraging, but have only been tested in vitro or in animal studies and further research is needed in order to conclude on how therapeutic strategies modulating ADMA actions can affect atherosclerosis progression and cardiovascular diseases.

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Effects of Rosuvastatin on Serum Asymmetric Dimethylarginine Levels and Atrial Structural Remodeling in Atrial Fibrillation Dogs

Abstract: A short course of rosuvastatin treatment decreased apoptosis and prevented atrial structural remodeling in association with a decrease in ADMA levels in AF dogs.

Cited by 12 publications

References 31 publications

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

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

Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing

Asymmetric Dimethylarginine: Clinical Significance and Novel Therapeutic Approaches

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