X-Chromosome-Linked miRNAs Regulate Sex Differences in Cardiac Physiology.

IF 16.5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation research Pub Date : 2025-01-31 Epub Date: 2024-12-30 DOI:10.1161/CIRCRESAHA.124.325447

James I Emerson, Wei Shi, Jose Paredes-Larios, William G Walker, Josiah E Hutton, Ileana M Cristea, William F Marzluff, Frank L Conlon

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Abstract

Background: Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states.

Methods: We identified microRNAs (miRNAs/miR) with sex-differential expression in mouse hearts.

Results: Four conserved miRNAs are present in a single locus on the X-chromosome and are expressed at higher levels in females than males. We show miRNA, miR-871, is responsible for decreased expression of the protein SRL (sarcalumenin) in females. SRL is involved in calcium signaling, and we show it contributes to differences in electrophysiology between males and females. miR-871 overexpression mimics the effects of the cardiac physiology of conditional cardiomyocyte-specific Srl-null mice. Inhibiting miR-871 with an antagomir in females shortened ventricular repolarization. The human orthologue of miR-871, miR-888, coevolved with the SRL 3' untranslated region and regulates human SRL.

Conclusions: These data highlight the importance of sex-differential miRNA mechanisms in mediating sex-specific functions and their potential relevance to human cardiac diseases.

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x染色体相关的mirna调节心脏生理的性别差异。

背景：男性和女性表现出不同的心脏解剖和功能特征，使他们易患特定的疾病状态。方法：我们鉴定了小鼠心脏中具有性别差异表达的microRNA （miRNAs/miR）。结果：4个保守的mirna存在于x染色体上的单个位点上，并且在女性中的表达水平高于男性。我们发现miRNA， miR-871，在女性中负责降低SRL（肌钙蛋白）的表达。SRL参与钙信号传导，我们发现它导致了男性和女性在电生理上的差异。miR-871过表达模拟条件心肌细胞特异性Srl-null小鼠心脏生理的影响。用阿塔戈莫抑制miR-871可缩短女性心室复极。miR-871的人类同源物miR-888与srl3 '非翻译区共同进化并调节人类SRL。结论：这些数据强调了性别差异miRNA机制在介导性别特异性功能中的重要性及其与人类心脏疾病的潜在相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Circulation research 医学-外周血管病

CiteScore

29.60

自引率

2.00%

发文量

535

审稿时长

3-6 weeks

期刊介绍： Circulation Research is a peer-reviewed journal that serves as a forum for the highest quality research in basic cardiovascular biology. The journal publishes studies that utilize state-of-the-art approaches to investigate mechanisms of human disease, as well as translational and clinical research that provide fundamental insights into the basis of disease and the mechanism of therapies. Circulation Research has a broad audience that includes clinical and academic cardiologists, basic cardiovascular scientists, physiologists, cellular and molecular biologists, and cardiovascular pharmacologists. The journal aims to advance the understanding of cardiovascular biology and disease by disseminating cutting-edge research to these diverse communities. In terms of indexing, Circulation Research is included in several prominent scientific databases, including BIOSIS, CAB Abstracts, Chemical Abstracts, Current Contents, EMBASE, and MEDLINE. This ensures that the journal's articles are easily discoverable and accessible to researchers in the field. Overall, Circulation Research is a reputable publication that attracts high-quality research and provides a platform for the dissemination of important findings in basic cardiovascular biology and its translational and clinical applications.