{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T16:38:36Z","timestamp":1764175116505,"version":"3.41.2"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"17","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2021,9,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Stress has emerged as an important risk factor for heart disease in women. Stress levels have been shown to correlate with delayed recovery and increased mortality after a myocardial infarction. Therefore, we sought to investigate if the observed sex\u2010specific effects of stress in myocardial infarction may be partly attributed to genomic interactions between the female sex hormones, estrogen (E2), and the primary stress hormones glucocorticoids.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Genomewide studies show that glucocorticoids inhibit estrogen\u2010mediated regulation of genes with established roles in cardiomyocyte homeostasis. These include\n              <jats:italic>5\u2010HT2BR<\/jats:italic>\n              (cardiac serotonin receptor 2B), the expression of which is critical to prevent cardiomyocyte death in the adult heart. Using siRNA, gene expression, and chromatin immunoprecipitation assays, we found that\n              <jats:italic>5\u2010HT2BR<\/jats:italic>\n              is a primary target of the glucocorticoid receptor and the estrogen receptor \u03b1 at the level of transcription. The glucocorticoid receptor blocks the recruitment of estrogen receptor \u03b1 to the promoter of the\n              <jats:italic>5\u2010HT2BR<\/jats:italic>\n              gene, which may contribute to the adverse effects of stress in the heart of premenopausal women. Using immunoblotting, TUNEL (terminal deoxynucleotidal transferase\u2013mediated biotin\u2013deoxyuridine triphosphate nick\u2010end labeling), and flow cytometry, we demonstrate that estrogen decreases cardiomyocyte death by a mechanism relying on\n              <jats:italic>5\u2010HT2BR<\/jats:italic>\n              expression. In vitro and in vivo experiments show that glucocorticoids inhibit estrogen cardioprotection in response to hypoxia\/reoxygenation injury and exacerbate the size of the infarct areas in myocardial infarction.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">These results established a novel mechanism underlying the deleterious effects of stress on female cardiac health in the setting of ischemia\/reperfusion.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.015868","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T09:08:26Z","timestamp":1630573706000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Glucocorticoid Inhibition of Estrogen Regulation of the Serotonin Receptor 2B in Cardiomyocytes Exacerbates Cell Death in Hypoxia\/Reoxygenation Injury"],"prefix":"10.1161","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4120-4910","authenticated-orcid":false,"given":"Hemangini A.","family":"Dhaibar","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center Shreveport LA"},{"name":"Center for Cardiovascular Diseases and Sciences Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie G.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center Shreveport LA"},{"name":"Center for Cardiovascular Diseases and Sciences Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shripa","family":"Amatya","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center Shreveport LA"},{"name":"Center for Cardiovascular Diseases and Sciences Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7724-5124","authenticated-orcid":false,"given":"Lilly","family":"Kamberov","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center Shreveport LA"},{"name":"Center for Cardiovascular Diseases and Sciences Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pranshu","family":"Khanna","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology Louisiana State University Health Sciences Center Shreveport LA"},{"name":"Center for Cardiovascular Diseases and Sciences Louisiana State University Health Sciences Center Shreveport LA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-213X","authenticated-orcid":false,"given":"A. 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