{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:06:46Z","timestamp":1789110406205,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["21JR1RA168"],"award-info":[{"award-number":["21JR1RA168"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460086"],"award-info":[{"award-number":["82460086"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82160089"],"award-info":[{"award-number":["82160089"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Heart failure with preserved ejection fraction (HFpEF) is prevalent among postmenopausal women and is strongly linked to estrogen deficiency. G\u2010protein coupled estrogen receptor (GPER) mediates non\u2010genomic estrogen signalling and exerts cardiovascular protective effects. Its role in the pathogenesis of HFpEF remains unclear. This study aimed to explore whether GPER activation could attenuate mitochondrial dysfunction and cardiac damage in ovariectomized (OVX) mice with HFpEF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Circulating GPER levels were measured in postmenopausal women with HFpEF and healthy controls. A correlation analysis was performed to assess the associations between GPER and cardiac function. Female C57BL\/6J mice underwent ovariectomy and were fed with high\u2010fat diet and\n                      <jats:sc>l<\/jats:sc>\n                      \u2010NAME to induce HFpEF. Mice were treated with the GPER agonist G\u20101 for 4\u00a0weeks. Cardiac function, histological changes, oxidative stress, mitochondrial function and mitophagy were evaluated\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum GPER levels were significantly higher in postmenopausal women with HFpEF and correlated with NT\u2010proBNP and E\/e\u2032. In OVX mice with HFpEF, GPER expression was up\u2010regulated, and G\u20101 improved diastolic function, reduced myocardial hypertrophy and oxidative stress. Importantly, G\u20101 restored mitochondrial ATP production, normalized mitochondrial dynamics and promoted mitophagy\n                      <jats:italic>in vivo<\/jats:italic>\n                      and\n                      <jats:italic>in vitro<\/jats:italic>\n                      . These effects were associated with activation of the AMPK\/ULK1 pathway. Inhibition of AMPK diminished the protective effects of G\u20101 in cardiomyocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>GPER agonist G\u20101 ameliorated mitochondrial dysfunction, promoted mitophagy and alleviated cardiac diastolic dysfunction in OVX mice with HFpEF, partially through the AMPK\/ULK1 pathway, indicating GPER as a therapeutic target for postmenopausal women with HFpEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70661","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T06:26:15Z","timestamp":1789107975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GPER stimulation attenuates mitochondrial dysfunction and cardiac dysfunction in ovariectomized mice with heart failure with preserved ejection 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