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.
Highlights
IntroductionWe show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia
Pathophysiological roles of cardiac dopamine system remain unknown
A decade ago, a large clinical study demonstrated that the prognosis of patients with chronic heart failure was worsened by the treatment with dopamine receptor agonists and suggested that ventricular arrhythmia might be related to the poor prognosis[7,8]
Summary
We show the role of dopamine D1 receptor (D1R)-expressing cardiomyocytes (CMs) in triggering heart failure-associated ventricular arrhythmia. Cardiac D1R has the potential to become a therapeutic target for preventing heart failure-associated ventricular arrhythmia. Prevention of life-threatening ventricular arrhythmias, as well as cardiac dysfunction is critically important for improving the prognosis of the patients with heart failure[2,3,4]. A decade ago, a large clinical study demonstrated that the prognosis of patients with chronic heart failure was worsened by the treatment with dopamine receptor agonists and suggested that ventricular arrhythmia might be related to the poor prognosis[7,8]. We show that D1R-expressing CMs play critical roles in triggering heart failure-associated ventricular arrhythmia and clarified its molecular mechanisms
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