{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:40:09Z","timestamp":1780368009664,"version":"3.54.1"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003443","name":"Ministry of Education and Science of the Russian Federation","doi-asserted-by":"publisher","award":["122020300042\u20104"],"award-info":[{"award-number":["122020300042\u20104"]}],"id":[{"id":"10.13039\/501100003443","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Currently, there is no effective therapy for takotsubo syndrome (stress\u2010induced cardiac injury in humans) in the clinics. It has previously been shown that \u03b2<jats:sub>2<\/jats:sub>\u2010adrenergic receptor (\u03b2<jats:sub>2<\/jats:sub>\u2010AR) agonist formoterol reduces cardiomyocyte injury in experimental takotsubo syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The aim of this study was to investigate whether formoterol prevents apoptosis and necrosis of cardiomyocytes and endothelial cells in stress\u2010induced cardiomyopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Stress\u2010induced cardiac injury was induced by immobilization of rats for 2, 6, and 24\u2009hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The myocardium of stressed rats showed a reduction in contractility and histological manifestations of cardiomyocyte damage: karyopyknosis, perinuclear edema of cardiomyocytes and endothelial cells, and microcirculation disturbances augmented with extended exposure to stress. In addition, apoptosis of endothelial cells was detected 6\u00a0hours after the onset of stress and peaked at 24\u2009hours. Apoptosis of cardiomyocytes significantly gained only after 24\u2009hours of stress exposure. These morphological alterations were associated with increased levels of serum creatine kinase\u2010MB, syndecan\u20101, and thrombomodulin after 24\u2009hours of stress. Administration of \u03b2<jats:sub>2<\/jats:sub>\u2010AR agonist formoterol (50\u2009\u03bcg\/kg) four times during 24\u2010hour stress exposure led to the improvement in myocardial inotropy, decrease in the severity of histological signatures, reduction in the number of TUNEL\u2010positive cardiomyocytes, serum creatine kinase\u2010MB, syndecan\u20101, and thrombomodulin levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Present data suggest that apoptosis and necrosis of cardiomyocytes and necrosis of endothelial cells in stress\u2010induced cardiac injury can be mitigated by activation of the \u03b2<jats:sub>2<\/jats:sub>\u2010AR. However, formoterol did not eliminate completely cardiomyocyte apoptosis, histological alterations, or endothelium injury markers under stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/fcp.13026","type":"journal-article","created":{"date-parts":[[2024,7,3]],"date-time":"2024-07-03T10:44:05Z","timestamp":1720003445000},"page":"1116-1130","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The \u03b2<sub>2<\/sub>\u2010adrenergic receptor agonist formoterol attenuates necrosis and apoptosis in the rat myocardium under experimental stress\u2010induced cardiac injury"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-1928","authenticated-orcid":false,"given":"Natalia V.","family":"Naryzhnaya","sequence":"first","affiliation":[{"name":"Cardiology Research Institute, Tomsk National Research Medical Center Russian Academy of Sciences  Tomsk, Russia, 111a, Kievskaya str. 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