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.
摘要：
心房颤动（AF）常见于肺动脉高压（PH），而机制和治疗仍有待探索。TRPV2调节心血管系统的结构和功能;然而，很少注意它在房颤中的作用。这项研究旨在确定TRPV2是否参与PH诱导的AF以及TRPV2抑制剂曲尼司特对PH大鼠模型AF的影响。采用野百合碱（MCT）和SU5416/缺氧（SuHx）诱导的PH模型检测心房电生理参数。在PH建立前1天开始每日给予曲尼司特(TRPV2抑制剂)或盐水。PH增加了对AF的敏感性，TRPV2在右心房上调。与PH大鼠相比，曲尼司特降低房颤诱导性,延长ERP和APD;减轻心肺重塑,延长P波持续时间和P-R间期;部分逆转Cav1.2,Nav1.5,Kv4.3,Kv4.2,Kv1.5,Kir2.1,Kir3.1,Kir3.4等离子通道的下调;改善右心房纤维化(RA),扩大，和心肌肥厚;减少炎症细胞的积累;下调炎症指标如TNF-α,IL-1β,CXCL1和CXCL2；并抑制PI3K-AKT-NF-κB信号通路的激活。我们的结果表明，TRPV2参与PH诱导的AF，和TRPV2抑制剂曲尼司特预防PH诱导的RA重塑。TRPV2可能是PH诱导的AF的有希望的靶标。
