James I Emerson, Wei Shi, Jose Paredes-Larios, William G Walker, Josiah E Hutton, Ileana M Cristea, William F Marzluff, Frank L Conlon
{"title":"x染色体相关的mirna调节心脏生理的性别差异。","authors":"James I Emerson, Wei Shi, Jose Paredes-Larios, William G Walker, Josiah E Hutton, Ileana M Cristea, William F Marzluff, Frank L Conlon","doi":"10.1161/CIRCRESAHA.124.325447","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states.</p><p><strong>Methods: </strong>We identified microRNAs (miRNAs/miR) with sex-differential expression in mouse hearts.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>These data highlight the importance of sex-differential miRNA mechanisms in mediating sex-specific functions and their potential relevance to human cardiac diseases.</p>","PeriodicalId":10147,"journal":{"name":"Circulation research","volume":" ","pages":"258-275"},"PeriodicalIF":16.5000,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781965/pdf/","citationCount":"0","resultStr":"{\"title\":\"X-Chromosome-Linked miRNAs Regulate Sex Differences in Cardiac Physiology.\",\"authors\":\"James I Emerson, Wei Shi, Jose Paredes-Larios, William G Walker, Josiah E Hutton, Ileana M Cristea, William F Marzluff, Frank L Conlon\",\"doi\":\"10.1161/CIRCRESAHA.124.325447\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Males and females exhibit distinct anatomic and functional characteristics of the heart, predisposing them to specific disease states.</p><p><strong>Methods: </strong>We identified microRNAs (miRNAs/miR) with sex-differential expression in mouse hearts.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>These data highlight the importance of sex-differential miRNA mechanisms in mediating sex-specific functions and their potential relevance to human cardiac diseases.</p>\",\"PeriodicalId\":10147,\"journal\":{\"name\":\"Circulation research\",\"volume\":\" \",\"pages\":\"258-275\"},\"PeriodicalIF\":16.5000,\"publicationDate\":\"2025-01-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11781965/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Circulation research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1161/CIRCRESAHA.124.325447\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCRESAHA.124.325447","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/30 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
X-Chromosome-Linked miRNAs Regulate Sex Differences in Cardiac Physiology.
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.
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.
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