Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner
Aowen Zhuang, Anna C. Calkin, Shannen Lau, Helen Kiriazis, D. Donner, Yingying Liu, Simon T. Bond, Sarah C. Moody, Eleanor A.M. Gould, Timothy D. Colgan, Sergio Ruiz‐Carmona, Michael Inouye, Thomas Q. de Aguiar Vallim, Elizabeth J. Tarling, Gregory A. Quaife-Ryan, James E. Hudson, Enzo R. Porrello, Paul Gregorevic, Xiao‐Ming Gao, Xiao‐Jun Du, Julie R. McMullen, Brian G. Drew
Abstract
methods, we demonstrate that OIP5-AS1 is regulated during cardiac development in rodent and human models and in disease settings in mice. Using CRISPR, we engineered a global OIP5-AS1 knockout (KO) mouse and demonstrated that female KO mice develop exacerbated heart failure following cardiac pressure overload (transverse aortic constriction [TAC]) but male mice do not. RNA-sequencing of wild-type and KO hearts suggest that OIP5-AS1 regulates pathways that impact mitochondrial function. Thus, these findings highlight OIP5-AS1 as a gene of interest in sex-specific differences in mitochondrial function and development of heart failure.