@article{628ed289d0804d3db953055cb4cdbae2,
title = "Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner",
abstract = "Long 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 of in vitro and ex vivo 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.",
keywords = "Cardiovascular medicine, Molecular physiology, Transcriptomics",
author = "Aowen Zhuang and Calkin, \{Anna C.\} and Shannen Lau and Helen Kiriazis and Donner, \{Daniel G.\} and Yingying Liu and Bond, \{Simon T.\} and Moody, \{Sarah C.\} and Gould, \{Eleanor A.M.\} and Colgan, \{Timothy D.\} and Carmona, \{Sergio Ruiz\} and Michael Inouye and \{de Aguiar Vallim\}, \{Thomas Q.\} and Tarling, \{Elizabeth J.\} and Quaife-Ryan, \{Gregory A.\} and Hudson, \{James E.\} and Porrello, \{Enzo R.\} and Paul Gregorevic and Gao, \{Xiao Ming\} and Xiao-Jun Du and McMullen, \{Julie R.\} and Drew, \{Brian G.\}",
note = "Funding Information: We acknowledge funding support from the Victorian State Government OIS program to Baker Heart \& Diabetes Institute (BHDI). These studies were supported in part by funding from the National Health \& Medical Research Council (NHMRC) of Australia to B.G.D. and J.R.M. (APP1127336). B.G.D. and A.C.C. received funding from the National Heart Foundation of Australia, via the Future Leader Fellowship Scheme (101789 and 100067, respectively). J.R.M. and P.G. are Research Fellows of the NHMRC (APP1078985 and APP1117835, respectively). We acknowledge the use of facilities and technical assistance from the Monash Histology Platform, Department of Anatomy and Developmental Biology, Monash University, and use of the gene set enrichment analysis (GSEA) software, and Molecular Signature Database (MSigDB) (Subramanian et al. 2005). We thank all members of the Cardiac Hypertrophy, MMA, and LMCD laboratories at BHDI for their ongoing contributions. B.G.D. and J.R.M. conceived the study and wrote the manuscript. B.G.D. J.R.M. A.C.C. and X.J.D. designed the mouse studies and directed experimental analysis. B.G.D. J.R.M. A.C.C. A.Z. S.L. Y.L. S.T.B. S.C.M. E.A.M.G. and S.R.C. analyzed data and interpreted findings. B.G.D. S.L. J.R.M. H.K. Y.L. A.Z. D.G.D. X.M.G. and X.J.D. performed animal experiments and analyzed data. B.G.D. J.R.M. A.C.C. T.D.C. T.Q.A.V. E.J.T. J.E.H. G.Q.R. E.P. P.G. and M.I. provided resources, data analysis, experimental guidance, and reagents. All authors had the opportunity to read, edit, and identify points for clarification before submission. The authors declare they have no conflict of interest. Funding Information: We acknowledge funding support from the Victorian State Government OIS program to Baker Heart \& Diabetes Institute (BHDI). These studies were supported in part by funding from the National Health \& Medical Research Council ( NHMRC ) of Australia to B.G.D. and J.R.M. ( APP1127336 ). B.G.D. and A.C.C. received funding from the National Heart Foundation of Australia , via the Future Leader Fellowship Scheme ( 101789 and 100067 , respectively). J.R.M. and P.G. are Research Fellows of the NHMRC ( APP1078985 and APP1117835 , respectively). We acknowledge the use of facilities and technical assistance from the Monash Histology Platform, Department of Anatomy and Developmental Biology, Monash University, and use of the gene set enrichment analysis (GSEA) software, and Molecular Signature Database (MSigDB) ( Subramanian et al., 2005 ). We thank all members of the Cardiac Hypertrophy, MMA, and LMCD laboratories at BHDI for their ongoing contributions. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = jun,
day = "25",
doi = "10.1016/j.isci.2021.102537",
language = "English",
volume = "24",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier",
number = "6",
}
SDG 3 Good Health and Well-being