Altered coronary vascular function in a mouse model of Hypertrophic Cardiomyopathy

Abstract

Mice with the troponin T (TnT)‐I79N mutation, which is associated with hypertrophic cardiomyopathy in humans, develop arrhythmias during stress despite the absence of an overt anatomical substrate. The arrhythmias are linked to the occurrence of energy deprived regions in the ventricular myocardium, but the underlying mechanism is not completely understood. Preliminary data indicate that vascular dysfunction that results in ischemia is at least in part responsible for the regional energy deprivation. In this study we are investigated whether cardiac microvascular function is altered in TnT‐I79N mice.We isolated resistance arterioles from the hearts of troponinTnT‐I79N mice and non‐transgenic mice, and evaluated vasodilatory responses to endothelium‐dependent (flow) and endothelium‐independent (DeaNONOate) stimuli. Contractile responses to pressure (myogenic responsiveness) and endothelin were also assessed. Flow‐induced vasodilation was significantly increased in coronary arterioles from TnT‐I79N mice (maximal dilation 81±9%) as compared to coronary arterioles from non‐transgenic mice (maximal dilation 58±9%). Endothelium‐independent responses to DeaNONOate were not altered in coronary arterioles from TnT‐I79N mice. Contractile responses to endothelin were significantly reduced in arterioles from TnT‐I79N mice (44±6% in TnT‐I79N arterioles vs. 64±5% in non‐transgenic arterioles; P<0.01). Myogenic responses to increasing transmural pressure were not altered in arterioles from TnT‐I79N mice.Altogether, these data indicate heightened responsiveness of the endothelium of coronary resistance arterioles in the hearts of TnT‐I79N mice. Since the mutant protein is exclusively expressed in the cardiomyocytes, this indicates an indirect effect of the cardiomyocytes on the vasculature.Support or Funding InformationNIH R01 to Sabine HukeThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.