Renal Denervation Suppresses the Inducibility of Atrial Fibrillation in a Rabbit Model for Atrial Fibrosis

Wei, Yong; Xu, Juan; Zhou, Genqing; Chen, Songwen; Ouyang, Ping; Liu, Shaowen

doi:10.1371/journal.pone.0160634

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…[36][37][38] Our previous study clearly indicated that permanent ventricular pressure overload by AAC induces atrial remodelling, including hypertrophy, dilatation and fibrosis, and susceptibility to AF. 39 This is consistent with other observations that AAC induced atrial fibrosis and increased vulnerability to AF. 28,40 Atrial interstitial fibrosis provides a better understanding of the initiation, maintenance and progression of AF.…”

Section: Discussionsupporting

confidence: 93%

“…As a result, atrial non‐homogeneity in conduction contributes to the maintenance and progression of AF . Our previous study clearly indicated that permanent ventricular pressure overload by AAC induces atrial remodelling, including hypertrophy, dilatation and fibrosis, and susceptibility to AF . This is consistent with other observations that AAC induced atrial fibrosis and increased vulnerability to AF .…”

Section: Discussionsupporting

confidence: 89%

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MicroRNA‐30c suppresses the pro‐fibrogenic effects of cardiac fibroblasts induced by TGF‐β1 and prevents atrial fibrosis by targeting TGFβRII

Wang

Chen

et al. 2018

J Cellular Molecular Medi

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Atrial fibrosis serves as an important contributor to atrial fibrillation (AF). Recent data have suggested that microRNA‐30c (miR‐30c) is involved in fibrotic remodelling and cancer development, but the specific role of miR‐30c in atrial fibrosis remains unclear. The purpose of this study was to investigate the role of miR‐30c in atrial fibrosis and its underlying mechanisms through in vivo and in vitro experiments. Our results indicate that miR‐30c is significantly down‐regulated in the rat abdominal aortic constriction (AAC) model and in the cellular model of fibrosis induced by transforming growth factor‐β1 (TGF‐β1). Overexpression of miR‐30c in cardiac fibroblasts (CFs) markedly inhibits CF proliferation, differentiation, migration and collagen production, whereas decrease in miR‐30c leads to the opposite results. Moreover, we identified TGFβRII as a target of miR‐30c. Finally, transferring adeno‐associated virus 9 (AAV9)‐miR‐30c into the inferior vena cava of rats attenuated fibrosis in the left atrium following AAC. These data indicate that miR‐30c attenuates atrial fibrosis via inhibition of CF proliferation, differentiation, migration and collagen production by targeting TGFβRII, suggesting that miR‐30c might be a novel potential therapeutic target for preventing atrial fibrosis.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

MicroRNA‐30c suppresses the pro‐fibrogenic effects of cardiac fibroblasts induced by TGF‐β1 and prevents atrial fibrosis by targeting TGFβRII

Wang

Chen

et al. 2018

J Cellular Molecular Medi

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“…A number of experimental studies investigated the mechanism underlying the potential antiarrhythmic effects of RDN. As summarized in Table , these basic studies demonstrated that, beyond BP reduction, RDN can prevent atrial electrophysiological changes, reverse atrial electrical and structural remodeling further reduce AF inducibility and AF episodes via modulating renal sympathetic nervous activity . The favorable antiarrhythmic effects independent of BP lowering were also observed at human research level .…”

Section: Discussionmentioning

confidence: 83%

“…As summarized in Table 6, these basic studies demonstrated that, beyond BP reduction, RDN can prevent atrial electrophysiological changes, reverse atrial electrical and structural remodeling further reduce AF inducibility and AF episodes via modulating renal sympathetic nervous activity. [36][37][38][39][40][41][42][43][44][45][46][47][48][49] The favorable antiarrhythmic effects independent of BP lowering were also observed at human research level. 50 Collectively, these mechanism investigations provide in-depth and rational explanations for the positive clinical outcome of the present study.…”

Section: Adjunctive Role Of Rdn In Af-experimental Investigationsmentioning

confidence: 81%

Synergy of pulmonary vein isolation and catheter renal denervation in atrial fibrillation complicated with uncontrolled hypertension: Mapping the renal sympathetic nerve and pulmonary vein (the pulmonary vein isolation plus renal denervation strategy)?

Chen

Kiuchi

Yin

et al. 2019

Cardiovasc electrophysiol

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Introduction Disturbance of sympathetic and vagal nervous system participates in the pathogenesis of hypertension and atrial fibrillation (AF). Renal denervation (RDN) can modulate autonomic nervous activity and reduce blood pressure (BP) in hypertensive patients. We aimed to evaluate the effect of RDN combined with pulmonary vein isolation (PVI) in patients with AF and hypertension. Methods Clinical trials including randomized data comparing PVI plus RDN vs PVI alone were enrolled. Primary outcome was incidence of AF recurrence after procedure. Results A total of 387 patients, of them 252 were randomized and were enrolled. Mean age was 57 ± 10 years, 71% were male, and mean left ventricular ejection fraction was 57.4% ± 6.9%. Follow‐up for randomized data was 12 months. Overall comparison for primary outcome showed that PVI + RDN was associated with significantly lower AF recurrence as compared with PVI alone (35.8% vs 55.4%, P < 0.0001). This advantageous effect was consistently maintained among randomized patients (37.3% vs 61.9%, odds ratio = 0.37, P = 0.0001), and among patients with implanted devices for detection of AF recurrence (38.9% vs 61.6%, P = 0.007). Post‐hoc sensitivity and regression analysis demonstrated very good stability of this primary result. Pooled Kaplan‐Meier analysis further showed that PVI + RDN was associated with significantly higher freedom from AF recurrence as compared with PVI alone (log‐rank test, P = 0.001). Besides, RDN resulted in significant BP reduction without additionally increasing the risk of adverse events. Conclusions RDN may provide synergetic effects with PVI to reduce the burden of AF and improve BP control in patients with AF and uncontrolled hypertension.

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“…53 In animals, RDN decreased the inducibility of AF. 54 In humans, Pokushalov et al 55 compared pulmonary vein isolation (PVI) alone and in combination with RDN in a small cohort (n = 27) of hypertensive patients with AF. The addition of RDN decreased AF episodes compared with PVI alone (69% vs. 29%, P = 0.033).…”

Section: Renal Denervation For Hf and Arrhythmiasmentioning

confidence: 99%

Extra‐cardiac targets in the management of cardiometabolic disease: Device‐based therapies

et al. 2021

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Heart failure (HF) does not occur in a vacuum and is commonly defined and exacerbated by its co-morbid conditions. Neurohormonal imbalance and systemic inflammation are some of the key pathomechanisms of HF but also commonly encountered co-morbidities such as arterial hypertension, diabetes mellitus, cachexia, obesity and sleep-disordered breathing. A cornerstone of HF management is neurohormonal blockade, which in HF with reduced ejection fraction has been tied to a reduction in morbidity and mortality. Pharmacological treatment effective in patients with HF with reduced ejection fraction did not show substantial effects in HF with preserved ejection fraction. Here, we review novel device-based therapies using neuromodulation of extra-cardiac targets to treat cardiometabolic disease.

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Renal Denervation Suppresses the Inducibility of Atrial Fibrillation in a Rabbit Model for Atrial Fibrosis

Cited by 13 publications

References 30 publications

MicroRNA‐30c suppresses the pro‐fibrogenic effects of cardiac fibroblasts induced by TGF‐β1 and prevents atrial fibrosis by targeting TGFβRII

MicroRNA‐30c suppresses the pro‐fibrogenic effects of cardiac fibroblasts induced by TGF‐β1 and prevents atrial fibrosis by targeting TGFβRII

Synergy of pulmonary vein isolation and catheter renal denervation in atrial fibrillation complicated with uncontrolled hypertension: Mapping the renal sympathetic nerve and pulmonary vein (the pulmonary vein isolation plus renal denervation strategy)?

Extra‐cardiac targets in the management of cardiometabolic disease: Device‐based therapies

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