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.

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.

Details

Title
Cardiac dopamine D1 receptor triggers ventricular arrhythmia in chronic heart failure
Author
Yamaguchi Toshihiro 1 ; Sumida, Tomokazu S 2   VIAFID ORCID Logo  ; Nomura Seitaro 3 ; Satoh Masahiro 4   VIAFID ORCID Logo  ; Higo Tomoaki 5 ; Ito Masamichi 1 ; Ko, Toshiyuki 1 ; Fujita Kanna 1 ; Sweet, Mary E 6 ; Sanbe Atsushi 7 ; Yoshimi Kenji 8 ; Manabe Ichiro 9 ; Sasaoka Toshikuni 10 ; Taylor, Matthew R, G 11 ; Toko Haruhiro 12 ; Takimoto Eiki 1 ; Naito, Atsuhiko T 13   VIAFID ORCID Logo  ; Komuro Issei 1 

1  Graduate School of Medicine, The University of Tokyo, Department of Cardiovascular Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
2  Graduate School of Medicine, The University of Tokyo, Department of Cardiovascular Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Yale School of Medicine, Department of Neurology and Immunobiology, New Haven, USA (GRID:grid.47100.32) (ISNI:0000000419368710) 
3  Graduate School of Medicine, The University of Tokyo, Department of Cardiovascular Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Genome Science Division, Research Center for Advanced Science and Technologies, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
4  The University of Tokyo, Genome Science Division, Research Center for Advanced Science and Technologies, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); Chiba University Graduate School of Medicine, Department of Cardiovascular Medicine, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101) 
5  Osaka University Graduate School of Medicine, Department of Cardiovascular Medicine, Osaka, Japan (GRID:grid.136593.b) (ISNI:0000 0004 0373 3971) 
6  University of Colorado, Human Medical Genetics and Genomics, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564) 
7  Iwate Medical University, Department of Pharmacotherapeutics, School of Pharmacy, Morioka, Japan (GRID:grid.411790.a) (ISNI:0000 0000 9613 6383) 
8  Juntendo University Graduate School of Medicine, Department of Neurophysiology, Tokyo, Japan (GRID:grid.258269.2) (ISNI:0000 0004 1762 2738) 
9  Graduate School of Medicine, Chiba University, Department of Disease Biology and Molecular Medicine, Chiba, Japan (GRID:grid.136304.3) (ISNI:0000 0004 0370 1101) 
10  Brain Research Institute, Niigata University, Department of Comparative and Experimental Medicine, Niigata, Japan (GRID:grid.260975.f) (ISNI:0000 0001 0671 5144) 
11  University of Colorado, Human Medical Genetics and Genomics, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564); University of Colorado, Cardiovascular Institute and Adult Medical Genetics Program, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564) 
12  Graduate School of Medicine, The University of Tokyo, Department of Cardiovascular Medicine, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X); The University of Tokyo, Department of Advanced Translational Research and Medicine in Management of Pulmonary Hypertension, Tokyo, Japan (GRID:grid.26999.3d) (ISNI:0000 0001 2151 536X) 
13  Toho University, Department of Physiology, Faculty of Medicine, Tokyo, Japan (GRID:grid.265050.4) (ISNI:0000 0000 9290 9879) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-18128-x
ProQuest document ID
2438795851
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.