{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T23:57:16Z","timestamp":1792627036782,"version":"4.5.0"},"reference-count":67,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T00:00:00Z","timestamp":1717200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Clinical studies demonstrated beneficial effects of sodium-glucose-transporter 2 inhibitors on the risk of cardiovascular death in patients with heart failure with preserved ejection fraction (HFpEF). However, underlying processes for cardioprotection remain unclear. The present study focused on the impact of empagliflozin (Empa) on myocardial function in a rat model with established HFpEF and analyzed underlying molecular mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Obese ZSF1 (Zucker fatty and spontaneously hypertensive) rats were randomized to standard care (HFpEF, n=18) or Empa (HFpEF\/Empa, n=18). ZSF1 lean rats (con, n=18) served as healthy controls. Echocardiography was performed at baseline and after 4 and 8 weeks, respectively. After 8 weeks of treatment, hemodynamics were measured invasively, mitochondrial function was assessed and myocardial tissue was collected for either molecular and histological analyses or transmission electron microscopy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              In HFpEF Empa significantly improved diastolic function (E\/\u00e9: con: 17.5\u00b12.8; HFpEF: 24.4\u00b14.6;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001 versus con; HFpEF\/Empa: 19.4\u00b13.2;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.001 versus HFpEF). This was accompanied by improved hemodynamics and calcium handling and by reduced inflammation, hypertrophy, and fibrosis. Proteomic analysis demonstrated major changes in proteins involved in mitochondrial oxidative phosphorylation. Cardiac mitochondrial respiration was significantly impaired in HFpEF but restored by Empa (V\n              <jats:sub>max<\/jats:sub>\n              complex IV: con: 0.18\u00b10.07 mmol O\n              <jats:sub>2<\/jats:sub>\n              \/s\/mg; HFpEF: 0.13\u00b10.05 mmol O\n              <jats:sub>2<\/jats:sub>\n              \/s\/mg;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              &lt;0.041 versus con; HFpEF\/Empa: 0.21\u00b10.05 mmol O\n              <jats:sub>2<\/jats:sub>\n              \/s\/mg;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.012 versus HFpEF) without alterations of mitochondrial content. The expression of cardiolipin, an essential stability\/functionality-mediating phospholipid of the respiratory chain, was significantly decreased in HFpEF but reverted by Empa (con: 15.9\u00b11.7 nmol\/mg protein; HFpEF: 12.5\u00b11.8 nmol\/mg protein;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.002 versus con; HFpEF\/Empa: 14.5\u00b11.8 nmol\/mg protein;\n              <jats:italic toggle=\"yes\">P<\/jats:italic>\n              =0.03 versus HFpEF). Transmission electron microscopy revealed a reduced size of mitochondria in HFpEF, which was restored by Empa.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>The study demonstrates beneficial effects of Empa on diastolic function, hemodynamics, inflammation, and cardiac remodeling in a rat model of HFpEF. These effects were mediated by improved mitochondrial respiratory capacity due to modulated cardiolipin and improved calcium handling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.123.011107","type":"journal-article","created":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T09:00:47Z","timestamp":1717750847000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Empagliflozin Improves Diastolic Function in HFpEF by Restabilizing the Mitochondrial Respiratory Chain"],"prefix":"10.1161","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0003-6882","authenticated-orcid":true,"given":"Antje","family":"Schauer","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Heart Center Dresden - Laboratory of Experimental and Molecular Cardiology, Technische Universit\u00e4t Dresden, Germany (A.S., V.A., E.L., A.A., P.B., A.M., P.K.N.A., A.L., 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and Cardiology, Heart Center Dresden - Laboratory of Experimental and Molecular Cardiology, Technische Universit\u00e4t Dresden, Germany (A.S., V.A., E.L., A.A., P.B., A.M., P.K.N.A., A.L., E.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Augstein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Heart Center Dresden - Laboratory of Experimental and Molecular Cardiology, Technische Universit\u00e4t Dresden, Germany (A.S., V.A., E.L., A.A., P.B., A.M., P.K.N.A., A.L., E.B.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Barthel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Heart Center Dresden - Laboratory of Experimental and Molecular Cardiology, Technische Universit\u00e4t Dresden, Germany (A.S., V.A., E.L., A.A., P.B., A.M., P.K.N.A., A.L., 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