Yannick Smolenski, Natali Froese, Paolo Galuppo, Christopher Werlein, Anna Gigina, Steven R Talbot, Sergej Erschow, Dirk Wedekind, Robert Geffers, Norbert B Ghyselinck, Heike Bähre, Jan C Kamp, Lavinia Neubert, Melanie Ricke-Hoch, Johann Bauersachs, Christian Riehle
{"title":"维生素A缺乏可减轻stra6缺陷心脏缺血损伤后的心脏破裂。","authors":"Yannick Smolenski, Natali Froese, Paolo Galuppo, Christopher Werlein, Anna Gigina, Steven R Talbot, Sergej Erschow, Dirk Wedekind, Robert Geffers, Norbert B Ghyselinck, Heike Bähre, Jan C Kamp, Lavinia Neubert, Melanie Ricke-Hoch, Johann Bauersachs, Christian Riehle","doi":"10.3389/fcvm.2025.1626769","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Stimulated by retinoic acid gene 6 (STRA6) is a cell surface receptor that regulates cellular uptake of vitamin A metabolites and cardiac development. We hypothesized that <i>Stra6</i> expression attenuates ischemic injury-induced heart failure following myocardial infarction (MI) by vitamin A-dependent mechanisms.</p><p><strong>Methods: </strong>MI was induced in mice with <i>Stra6</i> germline deletion, vitamin A deficiency (VitAD) by combined <i>lecithin-retinol acyltransferase (Lrat)</i> germline deletion and feeding with a vitamin A-deficient diet. Contractile function was determined by transthoracic echocardiography, cardiac structure was assessed by histological analysis, and gene profiling was performed by RNA sequencing.</p><p><strong>Results: </strong><i>Stra6</i> deletion and VitAD did not impact contractile function and cardiac structure under basal conditions. <i>Stra6</i> deficiency resulted in myocardial rupture, with the majority of mice dying by 4 days post-MI, which additional VitAD attenuated. Interestingly, contractile function, mRNA expression of heart failure markers, and cardiac structure were not different between groups 3 days post-MI. Gene profiling 3 days post-MI revealed decreased Wnt signaling in <i>Stra6</i>-deficient relative to wildtype hearts, which was reversed by VitAD.</p><p><strong>Conclusion: </strong>The present study identifies an unexpected role for VitAD, which preserves Wnt signaling and attenuates cardiac rupture in <i>Stra6</i>-deficient hearts following ischemic injury.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1626769"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479519/pdf/","citationCount":"0","resultStr":"{\"title\":\"Vitamin A deficiency attenuates cardiac rupture in <i>Stra6-</i>deficient hearts following ischemic injury.\",\"authors\":\"Yannick Smolenski, Natali Froese, Paolo Galuppo, Christopher Werlein, Anna Gigina, Steven R Talbot, Sergej Erschow, Dirk Wedekind, Robert Geffers, Norbert B Ghyselinck, Heike Bähre, Jan C Kamp, Lavinia Neubert, Melanie Ricke-Hoch, Johann Bauersachs, Christian Riehle\",\"doi\":\"10.3389/fcvm.2025.1626769\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Stimulated by retinoic acid gene 6 (STRA6) is a cell surface receptor that regulates cellular uptake of vitamin A metabolites and cardiac development. We hypothesized that <i>Stra6</i> expression attenuates ischemic injury-induced heart failure following myocardial infarction (MI) by vitamin A-dependent mechanisms.</p><p><strong>Methods: </strong>MI was induced in mice with <i>Stra6</i> germline deletion, vitamin A deficiency (VitAD) by combined <i>lecithin-retinol acyltransferase (Lrat)</i> germline deletion and feeding with a vitamin A-deficient diet. Contractile function was determined by transthoracic echocardiography, cardiac structure was assessed by histological analysis, and gene profiling was performed by RNA sequencing.</p><p><strong>Results: </strong><i>Stra6</i> deletion and VitAD did not impact contractile function and cardiac structure under basal conditions. <i>Stra6</i> deficiency resulted in myocardial rupture, with the majority of mice dying by 4 days post-MI, which additional VitAD attenuated. Interestingly, contractile function, mRNA expression of heart failure markers, and cardiac structure were not different between groups 3 days post-MI. Gene profiling 3 days post-MI revealed decreased Wnt signaling in <i>Stra6</i>-deficient relative to wildtype hearts, which was reversed by VitAD.</p><p><strong>Conclusion: </strong>The present study identifies an unexpected role for VitAD, which preserves Wnt signaling and attenuates cardiac rupture in <i>Stra6</i>-deficient hearts following ischemic injury.</p>\",\"PeriodicalId\":12414,\"journal\":{\"name\":\"Frontiers in Cardiovascular Medicine\",\"volume\":\"12 \",\"pages\":\"1626769\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12479519/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Cardiovascular Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fcvm.2025.1626769\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cardiovascular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcvm.2025.1626769","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
Vitamin A deficiency attenuates cardiac rupture in Stra6-deficient hearts following ischemic injury.
Background: Stimulated by retinoic acid gene 6 (STRA6) is a cell surface receptor that regulates cellular uptake of vitamin A metabolites and cardiac development. We hypothesized that Stra6 expression attenuates ischemic injury-induced heart failure following myocardial infarction (MI) by vitamin A-dependent mechanisms.
Methods: MI was induced in mice with Stra6 germline deletion, vitamin A deficiency (VitAD) by combined lecithin-retinol acyltransferase (Lrat) germline deletion and feeding with a vitamin A-deficient diet. Contractile function was determined by transthoracic echocardiography, cardiac structure was assessed by histological analysis, and gene profiling was performed by RNA sequencing.
Results: Stra6 deletion and VitAD did not impact contractile function and cardiac structure under basal conditions. Stra6 deficiency resulted in myocardial rupture, with the majority of mice dying by 4 days post-MI, which additional VitAD attenuated. Interestingly, contractile function, mRNA expression of heart failure markers, and cardiac structure were not different between groups 3 days post-MI. Gene profiling 3 days post-MI revealed decreased Wnt signaling in Stra6-deficient relative to wildtype hearts, which was reversed by VitAD.
Conclusion: The present study identifies an unexpected role for VitAD, which preserves Wnt signaling and attenuates cardiac rupture in Stra6-deficient hearts following ischemic injury.
期刊介绍:
Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers?
At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.