Angiotensin II Type 1 Receptor Inhibition is Associated with Reduced Tachyarrhythmia-Induced Ventricular Interstitial Fibrosis in a Goat Atrial Fibrillation Model

Chrysostomakis, Stavros I.; Karalis, Ioannis; Simantirakis, Emmanuel N.; Koutsopoulos, Anastasios; Mavrakis, Hercules E.; Chlouverakis, Gregory; Vardas, Panos

doi:10.1007/s10557-007-6053-z

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…AngII participates in the development of AF -induced myocardial fibrosis through activation of AT 1 and AT 2 receptors 9-11. AT 1 receptor antagonism significantly attenuates fibrosis process of atrial fibrillation in dogs 37.…”

Section: Discussionmentioning

confidence: 99%

“…AngII may mediate the profibrotic responses including cell growth, inflammation, fibroblast proliferation and transformation, and extracellular matrix (ECM) deposition primarily through transforming growth factor-β 1 (TGF-β 1 ) 9-11. TGF-β 1 is expressed in the adult heart, where it is secreted by cardiomyocytes and myofibroblasts and retains in significant amounts in ECM as a latent cytokine.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Atrial Fibrillation Induces Myocardial Fibrosis Through Angiotensin II Type 1 Receptor–Specific Arkadia-Mediated Downregulation of Smad7

Gao

Peng

et al. 2011

Circulation Research

136

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Atrial Fibrillation Induces Myocardial Fibrosis Through Angiotensin II Type 1 Receptor–Specific Arkadia-Mediated Downregulation of Smad7

Gao

Peng

et al. 2011

Circulation Research

136

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“…3,7,8 However, it is not fully understood whether Ang II influences the electrical properties of the remodeled left atrium. In our study, the prolongation of AT during RES, which was observed in SHR Izm s, was not found in SHR Izm s treated with ARB (olmesartan), which may be related to the reverse remodeling action of ARB that prevents reentrant atrial arrhythmias.…”

Section: Discussionmentioning

confidence: 99%

Direct action of an angiotensin II receptor blocker on angiotensin II-induced left atrial conduction delay in spontaneously hypertensive rats

et al. 2009

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In this study, the inhibitory action of angiotensin II (Ang II) receptor blocker (ARB) on Ang II-induced conduction blocking in the left atrium was studied. Transmembrane action potentials and effective refractory period (ERP) were recorded from the left atrial trabeculae of spontaneously hypertensive rats (SHR Izm s) that had been treated with or without olmesartan medoxomil (AT1 receptor blocker, 3.0 mg kg À1 ) for 8 weeks before the recording. During rapid electrical stimulation (RES), changes in activation time (AT) and frequencies of the conduction block were studied under perfusion of Ang II (10 À8 M) or Ang II plus ARB (10 À7 M). Interstitial fibrosis in the left atrium was quantitatively assessed using histological sections. Although action potential parameters and ERP did not differ between the two groups when preparations were driven with a basic cycle length, an Ang II-induced conduction delay was observed during RES, and this was significantly suppressed in SHR Izm s treated with ARB (Po0.05). The Ang II-induced conduction block was also significantly reduced with perfusion of ARB (Po0.05). The interstitial fibrous area was significantly larger in untreated SHR Izm s than in treated animals (Po0.01). This antagonizing action of AT1 blockade might contribute to its non-antiarrhythmic therapeutic effect on atrial fibrillation because of its indirect and direct actions on the structural and functional remodeling of the left atrium.

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“…The most important pathological feature of AF is the accumulation and deposition of extracellular matrix proteins, particularly in collagen . Available evidence indicates that RAS plays an important role in collagen production in AF . Several studies have demonstrated that AngII increases collagen production in cultured cardiac fibroblasts in vitro.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that AngII increases collagen production in cultured cardiac fibroblasts in vitro. Additionally, AngII participates in the development of AF‐induced myocardial fibrosis through activation of AT1 receptors . Recent studies have demonstrated that ACE inhibitors can block AngII synthesis catalyzed by ACE but cannot block AngII synthesis catalyzed by chymase, such as that which occurs in cardiac myocytes .…”

Section: Discussionmentioning

confidence: 99%

Angiotensin‐Converting Enzyme‐2 Overexpression Improves Atrial Remodeling and Function in a Canine Model of Atrial Fibrillation

Zhou

Wang

Fan

et al. 2015

JAHA

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BackgroundAtrial fibrosis is an important factor in initiating and maintaining atrial fibrillation. The purpose of this study was to test the hypothesis that atrial angiotensin‐converting enzyme‐2 (ACE2) overexpression might inhibit atrial collagen accumulation and improve atrial remodeling in a canine atrial pacing model.Methods and ResultsThirty‐two mongrel dogs of both genders were divided randomly into 4 groups: sham‐operated, control, gene therapy with adenovirus‐enhanced green fluorescent protein (Ad‐EGFP), and gene therapy with Ad‐ACE2. All of the dogs in the control, Ad‐EGFP, and Ad‐ACE2 groups were paced at 450 bpm for a period of 14 days. The dogs in the sham group were instrumented without pacing. After 2 weeks, all of the dogs underwent a thoracotomy operation and received epicardial gene painting. On post–gene transfer day 21, the animals underwent electrophysiology, histology, and molecular studies. The percentage of fibrosis in the Ad‐ACE2 group was markedly lower than the percentage in the control and Ad‐EGFP groups. Compared with the other groups, ACE2 expression was increased significantly in the Ad‐ACE2 group. Compared with the sham and Ad‐ACE2 groups, the expression levels of transforming growth factor‐β1 and Smad3 were significantly higher in the Ad‐EGFP and control groups; however, the expression levels of Smad7 were lower in the atrial tissue as detected by Western blot and reverse transcription polymerase chain reaction.ConclusionsOur results demonstrate that the overexpression of ACE2 inhibits atrial collagen accumulation and improves left atrial remodeling and function in a canine model of atrial fibrillation. Thus, targeted gene ACE2 therapy provides a promising approach for the treatment of atrial fibrillation.

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Angiotensin II Type 1 Receptor Inhibition is Associated with Reduced Tachyarrhythmia-Induced Ventricular Interstitial Fibrosis in a Goat Atrial Fibrillation Model

Cited by 17 publications

References 37 publications

Atrial Fibrillation Induces Myocardial Fibrosis Through Angiotensin II Type 1 Receptor–Specific Arkadia-Mediated Downregulation of Smad7

Atrial Fibrillation Induces Myocardial Fibrosis Through Angiotensin II Type 1 Receptor–Specific Arkadia-Mediated Downregulation of Smad7

Direct action of an angiotensin II receptor blocker on angiotensin II-induced left atrial conduction delay in spontaneously hypertensive rats

Angiotensin‐Converting Enzyme‐2 Overexpression Improves Atrial Remodeling and Function in a Canine Model of Atrial Fibrillation

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