Angiotensin-converting enzyme-2 overexpression improves atrial electrical remodeling through TRPM7 signaling pathway

// Tingquan Zhou 1, * , Zhihua Han 1, * , Jun Gu 1 , Shaojie Chen 2 , Yuqi Fan 1 , Huili Zhang 1 , Yuehui Yin 3 , Junfeng Zhang 1 and Changqian Wang 1 1 Department of Cardiology, Shanghai Ninth People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China 2 Department of Cardiology, Shanghai First People’s Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China 3 Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China * These authors have contributed equally to this work Correspondence to: Junfeng Zhang, email: jfzhang_dr@163.com Changqian Wang, email: wangcq2m9h@sohu.com Keywords: angiotensin II, angiotensin-converting enzyme 2, atrial fibrillation, atrial electrical remodeling, transient receptor potential melastatin-7 Received: February 18, 2017     Accepted: July 17, 2017     Published: August 12, 2017 ABSTRACT Atrial electrical remodeling is an important factor in the development and persistence of atrial fibrillation. The aim of this study was to examine the effects of atrial angiotensin-converting enzyme-2 overexpression on atrial electrical remodeling and to elucidate the molecular mechanisms underlying these effects. Twenty-eight male and female dogs were randomly divided into the following 4 groups: a sham-operation group, a control group, an adenovirus-enhanced green fluorescent protein (Ad-EGFP) gene group and an Ad-ACE2 gene group. All dogs in the Ad-EGFP and Ad-ACE2 groups were rhythmized at 450 bpm for 14 days. Two weeks later, all the dogs underwent thoracotomy and epicardial gene painting. On day 21 after gene transfer, all the animals were subjected to electrophysiological and molecular studies. AF induction rates and durations were significantly increased in the control and Ad-EGFP groups compared to the sham-operated and Ad-ACE2 groups. Transient receptor potential melastatin 7 (TRPM7) expression levels in the Ad-EGFP and control groups were significantly higher than those in the sham-operated and Ad-ACE2 groups. Basal [Mg 2+ ] i was significantly decreased in siRNA transfected cells compared with control and non-silencing siRNA-transfected cells. Our results suggest that ACE2 overexpression suppresses atrial electrical remodeling and improves atrial function through the TRPM7 signaling pathway.