Cardiac-Specific Deletion of Orai3 Leads to Severe Dilated Cardiomyopathy and Heart Failure in Mice.

ABSTRACT: Background Orai3 is a mammalian-specific member of the Orai family (Orai1‒3) and a component of the store-operated Ca²⁺ entry channels. There is little understanding of the role of Orai channels in cardiomyocytes, and its role in cardiac function remains unexplored. Thus, we developed mice lacking Orai1 and Orai3 to address their role in cardiac homeostasis. Methods and Results We generated constitutive and inducible cardiomyocyte-specific Orai3 knockout (Orai3^cKO) mice. Constitutive Orai3-loss led to ventricular dysfunction progressing to dilated cardiomyopathy and heart failure. Orai3^cKO mice subjected to pressure overload developed a fulminant dilated cardiomyopathy with rapid heart failure onset, characterized by interstitial fibrosis and apoptosis. Ult

SUBMITTER: Gammons J 

PROVIDER: S-EPMC8174158 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature