摘要：SummaryLong non-coding RNAs (lncRNAs) have been demonstrated to influence numerous biological processes, being strongly implicated in the maintenance and physiological function of various tissues including the heart. The lncRNA OIP5-AS1 (1700020I14Rik/Cyrano) has been studied in several settings; however its role in cardiac pathologies remains mostly uncharacterized. Using a series ofin vitroandex vivomethods, 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.Graphical abstractDisplay OmittedHighlights•The lncRNA OIP5-AS1 is enriched in striated muscles in mice and humans.•OIP5-AS1 is regulated during heart development and in models of heart disease.•Global deletion of OIP5-AS1 exacerbates heart failure specifically in female mice.•Transcriptomics analysis suggests that loss OIP5-AS1 alters mitochondrial function.Cardiovascular medicine; Molecular physiology; Transcriptomics
