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
  • 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: [email protected].
  • 4. Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China. Electronic address: [email protected].
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.
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