硝酰基脂肪酸通过维持钙稳态来抑制缺血性室性心律失常。

Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis.

机构信息

Clinic III for Internal Medicine, Department of Cardiology, Center for Molecular Medicine Cologne (CMMC), University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Center for Molecular Medicine Cologne, CMMC, University of Cologne, Cologne, Germany.

出版信息

Sci Rep. 2020 Sep 18;10(1):15319. doi: 10.1038/s41598-020-71870-6.

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca leak. NO-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO-OA might be a novel pharmacological option for the prevention of VT development.

硝酰基脂肪酸是一种具有亲电性的抗炎介质，在心肌缺血损伤过程中产生。这些物质在心肌缺血的急性期是否具有抗心律失常作用，目前尚未得到研究。本文中，我们证明了在心肌缺血的急性期，用 9- 和 10-硝代十八碳-9-烯酸（硝基油酸，NO-OA）预处理小鼠可显著降低发生急性室性心动过速（VT）的易感性。因此，心外膜标测显示心室传导的均匀性明显增强。NO-OA 处理分离的心肌细胞可降低肾上腺素能异丙肾上腺素刺激下自发性收缩的数量，并几乎消除了 Ryanodine receptor type 2 (RyR2)-依赖性肌浆网 Ca 渗漏。NO-OA 通过抑制 CaMKII 活性的增加还显著降低了 RyR2 磷酸化。因此，NO-OA 可能是预防 VT 发展的一种新的药理学选择。