{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T22:58:12Z","timestamp":1790290692420,"version":"4.1.0"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,4,9]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In spontaneously hypertensive rats (\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      ) we observed profound myocardial metabolic changes during early hypertension before development of cardiac dysfunction and left ventricular hypertrophy. In this study, we evaluated whether metformin improved myocardial metabolic abnormalities and simultaneously prevented contractile dysfunction and left ventricular hypertrophy in\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      and control Wistar\u2013Kyoto rats were treated with metformin from 2 to 5\u00a0months of age, when\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      hearts exhibit metabolic abnormalities and develop cardiac dysfunction and left ventricular hypertrophy. We evaluated the effect of metformin on myocardial glucose uptake rates with dynamic 2\u2010[\n                      <jats:sup>18<\/jats:sup>\n                      F] fluoro\u20102\u2010deoxy\u2010D\u2010glucose positron emission tomography. We used cardiac\n                      <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>\n                      in vivo to assess the effect of metformin on ejection fraction, left ventricular mass, and end\u2010diastolic wall thickness, and also analyzed metabolites,\n                      <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\n                      \u2010activated protein kinase and mammalian target\u2010of\u2010rapamycin activities, and mean arterial blood pressure. Metformin\u2010treated\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      had lower mean arterial blood pressure but remained hypertensive. Cardiac glucose uptake rates, left ventricular mass\/tibia length, wall thickness, and circulating free fatty acid levels decreased to normal, and ejection fraction improved in treated\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      . Hearts of treated\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      exhibited increased\n                      <jats:styled-content style=\"fixed-case\">AMP<\/jats:styled-content>\n                      \u2010activated protein kinase phosphorylation and reduced mammalian target\u2010of\u2010rapamycin activity. Cardiac metabolite profiling demonstrated that metformin decreased fatty acyl carnitines and markers of oxidative stress in\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Metformin reduced blood pressure, normalized myocardial glucose uptake, prevented left ventricular hypertrophy, and improved cardiac function in\n                      <jats:styled-content style=\"fixed-case\">SHR<\/jats:styled-content>\n                      . Metformin may exert its effects by normalizing myocardial\n                      <jats:styled-content style=\"fixed-case\">AMPK<\/jats:styled-content>\n                      and mammalian target\u2010of\u2010rapamycin activities, improving fatty acid oxidation, and reducing oxidative stress. Thus, metformin may be a new treatment to prevent or ameliorate chronic hypertension\u2013induced left ventricular hypertrophy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.119.015154","type":"journal-article","created":{"date-parts":[[2020,4,4]],"date-time":"2020-04-04T05:00:47Z","timestamp":1585976447000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Metformin Improves Cardiac Metabolism and Function, and Prevents Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats"],"prefix":"10.1161","volume":"9","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Min\u0107zuk","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"},{"name":"Department of Experimental Physiology and Pathophysiology Medical University of Bia\u0142ystok Bia\u0142ystok Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Massey","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"},{"name":"Department of Biomedical Engineering University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Howell","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Jack","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumen","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Patrie","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Kramer","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick H.","family":"Epstein","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert M.","family":"Carey","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Taegtmeyer","sequence":"additional","affiliation":[{"name":"McGovern Medical School The University of Texas Health Science Center, Houston, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3089-7766","authenticated-orcid":false,"given":"Susanna R.","family":"Keller","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism Department of Medicine University of Virginia Charlottesville VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2683-9165","authenticated-orcid":false,"given":"Bijoy K.","family":"Kundu","sequence":"additional","affiliation":[{"name":"Department of Radiology and Medical Imaging University of Virginia Charlottesville VA"},{"name":"Department of Biomedical Engineering University of Virginia Charlottesville VA"},{"name":"Cardiovascular Research Center University of Virginia Charlottesville 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