2. Academic Validation
  3. TRPV2 inhibitor tranilast prevents atrial fibrillation in rat models of pulmonary hypertension

TRPV2 inhibitor tranilast prevents atrial fibrillation in rat models of pulmonary hypertension

  • Cell Calcium. 2023 Dec 21:117:102840. doi: 10.1016/j.ceca.2023.102840.
Tianxin Ye 1,  Zhuonan Song 1,  Yunping Zhou 1,  Zhangchi Liu 2,  Yi Yu 2,  Fangcong Yu 1,  Yanan Chu 1,  Jiaran Shi 1,  Longbo Wang 1,  Cui Zhang 2,  Xin Liu 2,  Bo Yang 2,  Jinxiu Yang 3,  Xingxiang Wang 4
Affiliations

Affiliations

  • 1 Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
  • 2 Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China.
  • 3 Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address: 1320099@zju.edu.cn.
  • 4 Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address: 1304016@zju.edu.cn.
PMID: 38160478 DOI: 10.1016/j.ceca.2023.102840
Abstract

Atrial fibrillation (AF) is common in pulmonary hypertension (PH), whereas the mechanisms and treatments remain to be explored. TRPV2 regulates the structure and function of the cardiovascular system; however, little attention has been given to its role in AF. This study was to determine whether TRPV2 was involved in PH-induced AF and the effects of TRPV2 inhibitor tranilast on AF in rat models of PH. Monocrotaline (MCT) and SU5416/hypoxia (SuHx)-induced PH models were performed to detect atrial electrophysiological parameters. Daily tranilast (a TRPV2 inhibitor) or saline was given starting 1 day before PH establishment. PH increased the susceptibility to AF, with TRPV2 up-regulated in the right atria. Compared to PH rats, tranilast reduced AF inducibility and the prolongations of ERP and APD; mitigated cardiopulmonary remodeling and the increases in P-wave duration and P-R interval; partially reversed the down-regulation of ion channels such as Cav1.2, Nav1.5, Kv4.3, Kv4.2, Kv1.5, Kir2.1, Kir3.1, Kir3.4 as well as connexin (Cx) 40 and Cx43; improved right atrial (RA) fibrosis, enlargement, and myocardial hypertrophy; decreased the accumulation of inflammatory cells; down-regulated inflammatory Indicators such as TNF-α, IL-1β, CXCL1, and CXCL2; and inhibited the activation of the PI3K-AKT-NF-κB signaling pathway. Our results reveal that TRPV2 participates in PH-induced AF, and TRPV2 inhibitor tranilast prevents PH-induced RA remodeling. TRPV2 might be a promising target for PH-induced AF.

Keywords

Atrial remodeling; Inflammation; Pulmonary hypertension; TRPV2.

Figures
Products