Circadian and sleep disruptions have been shown to lead to an increased risk for cardiovascular (CV) events. Huntington’s disease (HD) patients are reported to have various symptoms including circadian and motor deficits. In addition, CV symptoms are implicated as the cause of death in over 30% of the HD patient population. However, very little is understood about the intersection between circadian disruption, CV disease, and HD. Here we utilized two mouse models, BACHD and Q175, to investigate CV pathology in HD. Reduced diurnal and circadian resting heart rate rhythms, heart rate variability, and baroreceptor reflex support that the autonomic regulation of the CV system is compromised in both HD mouse lines. In addition, age-dependent reduction in the heart function and cardiac fibrosis were observed. These results led us to test the hypothesis that reducing the mutant huntingtin (mHtt) expression in the cardiomyocytes is sufficient to rescue CV symptoms seen in BACHD mice by crossing with the cardiomyocyte-specific Cre, Myh6-Cre. Our results show that reduced mHtt expression in the cardiomyocytes help improve left ventricular ejection fraction, several heart disease markers, and grip strength, a behavioral marker of cardiovascular health in the BACHD mice. Together this data indicates that heart disease in HD patients is likely to be driven both by cardiomyocyte specific pathology as well as dysfunction in the ANS
