Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
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DOI：
10.1038/s41467-020-18128-x
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发表时间：
2020-08-31
影响因子：
16.6
通讯作者：
Komuro, Issei
中科院分区：
文献类型：
--
作者：
Yamaguchi, Toshihiro;Sumida, Tomokazu S.;Komuro, Issei
心脏多巴胺系统的病理生理作用仍然未知。在这里，我们显示多巴胺D1受体（D1R）表达心肌细胞（CM）在触发心力衰竭相关的室性心律失常的作用。全面的单细胞分辨率分析确定了心力衰竭模型小鼠和持续性室性心动过速心力衰竭患者中D1R表达CM的存在。CM中D1R的过表达干扰正常的钙处理，而CM特异性D1R缺失改善心力衰竭相关的室性心律失常。因此，心脏D1R有可能成为预防心力衰竭相关室性心律失常的治疗靶点。多巴胺D1受体（D1R）在慢性心力衰竭中的病理生理作用仍不清楚。在这里，作者表明，表达D1R的心肌细胞出现在慢性心力衰竭中，并在触发致命性室性心律失常中发挥关键作用。
Pathophysiological roles of cardiac dopamine system remain unknown. Here, we show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia. Comprehensive single-cell resolution analysis identifies the presence of D1R-expressing CMs in both heart failure model mice and in heart failure patients with sustained ventricular tachycardia. Overexpression of D1R in CMs disturbs normal calcium handling while CM-specific deletion of D1R ameliorates heart failure-associated ventricular arrhythmia. Thus, cardiac D1R has the potential to become a therapeutic target for preventing heart failure-associated ventricular arrhythmia. The pathophysiological role of dopamine D1 receptor (D1R) in chronic heart failure remains elusive. Here the authors show that D1R-expressing cardiomyocytes appear in chronic heart failure and play a pivotal role in triggering lethal ventricular arrhythmias.