TRPV2 Inhibition Prevents Right Ventricular Remodeling and Arrhythmia in Experimental Pulmonary Hypertension

作者：Zhuonan Song, Tianxin Ye, Yunping Zhou, Fangcong Yu, Longbo Wang, Cui Zhang, Bo Yang, Bin Chen, Yutao Wu, Jinxiu Yang, Xingxiang Wang · 发表于：The FASEB Journal · 年份：2025 · DOI：10.1096/fj.202501356rr · 被引用次数：2 · 研究领域：Cardiac electrophysiology and arrhythmias、Cardiovascular Function and Risk Factors、Cardiovascular Effects of Exercise

Right ventricular (RV) failure and malignant arrhythmia are determinants of the prognosis of pulmonary arterial hypertension (PAH). Transient receptor potential vanilloid type 2 (TRPV2) is involved in the development of heart failure, whereas its role in PAH deserves further exploration. This study aimed to explore whether TRPV2 contributes to SU5416/hypoxia (SuHx)-induced ventricular remodeling and arrhythmias, and its possible mechanisms. Haemodynamic measurements, electrocardiogram, ventricular electrophysiological protocol, Wheat germ agglutinin (WGA) staining, hematoxylin and eosin (H&E) staining, Masson trichrome staining, immunofluorescence, real-time quantitative PCR (qPCR) and western blot were performed. Meanwhile, small interfering RNA (siRNA) for targeting TRPV2 or β-catenin was used to further verify the potential mechanism of TRPV2. In the SuHx-induced PH rat model, TRPV2 inhibitor tranilast significantly reduced mean pulmonary artery pressure (mPAP) and pulmonary vascular remodeling; relieved ventricular remodeling, myocardial fibrosis, and hypertrophy; shortened the prolongation of QT, QTc, Tpeak-Tend interval, effective refractory period (ERP) and action potential duration (APD); reduced susceptibility to ventricular fibrillation (VF). TRPV2 inhibition restored calcium homeostasis, attenuated ion channel and connexin remodeling (Kv4.3, Kv4.2, Kv1.5, Kir3.1, Kir3.4, KCNK3, Cx40 and Cx43), prevented autonomic dysfunction, reduced ventricular fibrosis, and infla...