白细胞介素-1β、氧化应激与钙处理异常介导糖尿病性心律失常风险。

Interleukin-1β, Oxidative Stress, and Abnormal Calcium Handling Mediate Diabetic Arrhythmic Risk.

作者信息

Liu Hong, Zhao Yang, Xie An, Kim Tae-Yun, Terentyeva Radmila, Liu Man, Shi Guangbin, Feng Feng, Choi Bum-Rak, Terentyev Dmitry, Hamilton Shanna, Dudley Samuel C

机构信息

Division of Cardiology, Department of Medicine, Lillehei Heart Institute, University of Minnesota Twin Cities, Minneapolis, Minnesota, USA.

Division of Cardiology, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, China.

出版信息

JACC Basic Transl Sci. 2021 Jan 20;6(1):42-52. doi: 10.1016/j.jacbts.2020.11.002. eCollection 2021 Jan.

Diabetes mellitus (DM) is associated with increased arrhythmia. Type 2 DM (T2DM) mice showed prolonged QT interval and increased ventricular arrhythmic inducibility, accompanied by elevated cardiac interleukin (IL)-1β, increased mitochondrial reactive oxygen species (mitoROS), and oxidation of the sarcoplasmic reticulum (SR) Ca release channel (ryanodine receptor 2 [RyR2]). Inhibiting IL-1β and mitoROS reduced RyR2 oxidation and the ventricular arrhythmia in DM. Inhibiting SR Ca2 leak by stabilizing the oxidized RyR2 channel reversed the diabetic arrhythmic risk. In conclusion, cardiac IL-1β mediated the DM-associated arrhythmia through mitoROS generation that enhances SR Ca leak. The mechanistic link between inflammation and arrhythmias provides new therapeutic options.