New role for cardiomyocyte Bmal1 in the regulation of sex-specific heart transcriptomes.

Autor: Zhang X; Department of Physiology and Aging, University of Florida, Gainesville FL, United States.; These authors contributed equally to this paper., Procopio SB; Department of Physiology and Aging, University of Florida, Gainesville FL, United States.; These authors contributed equally to this paper., Ding H; Department of Biostatics, University of Florida, Gainesville FL, United States., Semel MG; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Schroder EA; Department of Physiology, University of Kentucky, Lexington, KY, United States.; Department of Internal Medicine, University of Kentucky, Lexington, KY, United States., Seward TS; Department of Physiology, University of Kentucky, Lexington, KY, United States., Du P; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Wu K; Department of Physiology and Aging, University of Florida, Gainesville FL, United States., Johnson SR; Department of Physiology, University of Kentucky, Lexington, KY, United States., Prabhat A; Department of Physiology, University of Kentucky, Lexington, KY, United States., Schneider DJ; Department of Physiology, University of Kentucky, Lexington, KY, United States., Stumpf IG; Department of Physiology, University of Kentucky, Lexington, KY, United States., Rozmus ER; Department of Physiology, University of Kentucky, Lexington, KY, United States., Huo Z; Department of Biostatics, University of Florida, Gainesville FL, United States., Delisle BP; Department of Physiology, University of Kentucky, Lexington, KY, United States., Esser KA; Department of Physiology and Aging, University of Florida, Gainesville FL, United States.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Apr 21. Date of Electronic Publication: 2024 Apr 21.
DOI: 10.1101/2024.04.18.590181
Abstrakt: It has been well established that cardiovascular diseases exhibit significant differences between sexes in both preclinical models and humans. In addition, there is growing recognition that disrupted circadian rhythms can contribute to the onset and progression of cardiovascular diseases. However little is known about sex differences between the cardiac circadian clock and circadian transcriptomes in mice. Here, we show that the the core clock genes are expressed in common in both sexes but the circadian transcriptome of the mouse heart is very sex-specific. Hearts from female mice expressed significantly more rhythmically expressed genes (REGs) than male hearts and the temporal pattern of REGs was distinctly different between sexes. We next used a cardiomyocyte-specific knock out of the core clock gene, Bmal1 , to investigate its role in sex-specific gene expression in the heart. All sex differences in the circadian transcriptomes were significantly diminished with cardiomyocyte-specific loss of Bmal1 . Surprisingly, loss of cardiomyocyte Bmal1 also resulted in a roughly 8-fold reduction in the number of all the differentially expressed genes between male and female hearts. We conclude that cardiomyocyte-specific Bmal1 , and potentially the core clock mechanism, is vital in conferring sex-specific gene expression in the adult mouse heart.
Databáze: MEDLINE
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