2020.09.24
Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
(Nat Commun. 2020 Aug 31;11(1):4364. doi: 10.1038/s41467-020-18128-x.)
Yamaguchi T1, Sumida TS1,2, Nomura S1,3, Satoh M3,4, Higo T5, Ito M1, Ko T1, Fujita K1, Sweet ME6, Sanbe A7, Yoshimi K8, Manabe I9, Sasaoka T10, Taylor MRG6,11, Toko H1,12, Takimoto E1, Naito AT13, Komuro I14.
1Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.
2Department of Neurology and Immunobiology, Yale School of Medicine, USA.
3Genome Science Division, Research Center for Advanced Science and Technologies, The University of Tokyo.
4Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine.
5Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine.
6Human Medical Genetics and Genomics, University of Colorado, USA.
7Department of Pharmacotherapeutics, School of Pharmacy, Iwate Medical University.
8Department of Neurophysiology, Juntendo University Graduate School of Medicine.
9Department of Disease Biology and Molecular Medicine, Graduate School of Medicine, Chiba University.
10Department of Comparative and Experimental Medicine, Brain Research Institute, Niigata University.
11Cardiovascular Institute and Adult Medical Genetics Program, University of Colorado, USA.
12Department of Advanced Translational Research and Medicine in Management of Pulmonary Hypertension, The University of Tokyo.
13Department of Physiology, Faculty of Medicine, Toho University.
14Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo.
Overview
Prof. Toshikuni Sasaoka at Brain Research Institute, Niigata University has collaborated with Specially Appointed Assistant Prof. Toshihiro Yamaguchi, Seitaro Nomura and Prof. Issei Komuro at Dept. Cardiovascular Medicine of Tokyo University Hospital, as well as Prof. Atsushi Naito at Toho University School of Medicine and Assistant Prof. Tomokazu Sumida at Yale University Medical School. By focusing on the role of cardiac dopamine receptors in the heart, which had previously been uncovered, they have discovered for the first time that these receptors contribute to the development of fatal arrhythmias in the setting of heart failure.
Abstract
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.
