{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T10:49:34Z","timestamp":1767005374870,"version":"3.48.0"},"reference-count":44,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Anim Models and Exp Med"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endoplasmic reticulum (ER) stress is an important factor in the development of numerous cardiovascular disorders; nevertheless, the association between ER stress and mitral regurgitation (MR) remains inadequately characterized. The molecular mechanism of pimobendan (PIMO) that contributes to the delay in congestive heart failure (CHF) in MR associated with apoptosis and fibrosis is still unclear. Our aim was to examine the impact of PIMO on ER stress, apoptosis, and fibrosis in a chronic MR rat model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>MR was surgically induced in 10 Sprague\u2013Dawley rats, with 5 serving as sham operation controls. At 8\u2009weeks postsurgery, the MR animals were randomly allocated into two groups: MR and MR\u2009+\u2009PIMO groups. PIMO was administered twice daily through oral gavage for 4\u2009weeks, whereas the sham and MR groups were administered similar quantities of drinking water. Echocardiography was conducted before the delivery of PIMO as a baseline measure and at the end of the study. At the end of the investigation, hearts were procured for histopathological and ER stress evaluations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PIMO significantly maintained heart function and structural remodeling in the MR animals. PIMO significantly reduced MR\u2010induced myocyte apoptosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.044) and fibrosis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002) by reducing the messenger RNA expression of genes associated with ER stress (\n                      <jats:italic>GRP78<\/jats:italic>\n                      [glucose\u2010regulated protein 78],\n                      <jats:italic>ATF4<\/jats:italic>\n                      [activating transcription factor 4], and\n                      <jats:italic>CHOP<\/jats:italic>\n                      [C\/ERP homologous protein]) compared to the MR group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01, and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PIMO demonstrated cardioprotective benefits on heart function, myocyte apoptosis, and fibrosis by regulating ER stress in an MR\u2010induced CHF rat model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ame2.70093","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T04:59:50Z","timestamp":1762232390000},"page":"2069-2079","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pimobendan alleviates myocyte apoptosis and fibrosis associated with mitral regurgitation by targeting endoplasmic reticulum stress"],"prefix":"10.1002","volume":"8","author":[{"given":"Pakit","family":"Boonpala","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty 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