{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T19:19:42Z","timestamp":1790363982718,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The effects of the selective sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin in low dose on cardiac function were investigated in normoglycemic rats. Cardiac parameters were measured by intracardiac catheterization 30 min after intravenous application of empagliflozin to healthy animals. Empagliflozin increased the ventricular systolic pressure, mean pressure, and the max dP\/dt (p &lt; 0.05). Similarly, treatment with empagliflozin (1 mg\/kg, p.o.) for one week increased the cardiac output, stroke volume, and fractional shortening (p &lt; 0.05). Myocardial infarction (MI) was induced by ligation of the left coronary artery. On day 7 post MI, empagliflozin (1 mg\/kg, p.o.) improved the systolic heart function as shown by the global longitudinal strain (\u221221.0 \u00b1 1.1% vs. \u221216.6 \u00b1 0.7% in vehicle; p &lt; 0.05). In peri-infarct tissues, empagliflozin decreased the protein expression of matrix metalloproteinase 9 (MMP9) and favorably regulated the cardiac transporters sarco\/endoplasmic reticulum Ca2+-ATPase (SERCA2a) and sodium hydrogen exchanger 1 (NHE1). In H9c2 cardiac cells, empagliflozin decreased the MMP2,9 activity and prevented apoptosis. Empagliflozin did not alter the arterial stiffness, blood pressure, markers of fibrosis, and necroptosis. Altogether, short-term treatment with low-dose empagliflozin increased the cardiac contractility in normoglycemic rats and improved the systolic heart function in the early phase after MI. These effects are attributed to a down-regulation of MMP9 and NHE1, and an up-regulation of SERCA2a. This study is of clinical importance because it suggests that a low-dose treatment option with empagliflozin may improve cardiovascular outcomes post-MI. Down-regulation of MMPs could be relevant to many remodeling processes including cancer disease.<\/jats:p>","DOI":"10.3390\/ijms22115437","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"5437","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Low-Dose Empagliflozin Improves Systolic Heart Function after Myocardial Infarction in Rats: Regulation of MMP9, NHE1, and SERCA2a"],"prefix":"10.3390","volume":"22","author":[{"given":"Jana","family":"Goerg","sequence":"first","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Sommerfeld","sequence":"additional","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Greiner","sequence":"additional","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilyara","family":"Lauer","sequence":"additional","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Seckin","sequence":"additional","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"},{"name":"Department of Biotechnology, University of Applied Science, 13353 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kulikov","sequence":"additional","affiliation":[{"name":"Pavlov First Saint-Petersburg State Medical University, 197022 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Ivkin","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State Chemical-Pharmaceutical University, 197376 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Kintscher","sequence":"additional","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4294-5531","authenticated-orcid":false,"given":"Sergey","family":"Okovityi","sequence":"additional","affiliation":[{"name":"Saint-Petersburg State Chemical-Pharmaceutical University, 197376 Saint Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Kaschina","sequence":"additional","affiliation":[{"name":"Charite\u0301-Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Institute of Pharmacology, Center for Cardiovascular Research (CCR), 10115 Berlin, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, 10115 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","first-page":"1094","article-title":"Empagliflozin, cardiovascular outcomes, and mortality in Type 2 Diabetes","volume":"374","author":"Zinman","year":"2016","journal-title":"N. 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