{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T04:08:37Z","timestamp":1789013317387,"version":"build-2803163510"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Sodium glucose cotransporter 2 inhibitors may improve mitochondrial biogenesis and attenuate pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). We investigated the impact of empagliflozin in PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Microvascular endothelial cells (MVECs) were collected from the lungs of control patients and patients with PAH, and the effects of empagliflozin on MVECs were evaluated. Subsequently, treatment effects of empagliflozin (300 mg\/kg chow, n=12) or placebo (n=12) were evaluated in experimental PAH rats (SU5416 injection followed by 3\u2009weeks of hypoxia). In addition, we conducted a phase IIa proof\u2010of\u2010concept trial, EMPHOWER PoC (Feasibility Study of Empagliflozin as Treatment for Idiopathic Pulmonary Arterial Hypertension), to assess the feasibility of 12\u2009weeks of empagliflozin treatment in patients with PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In comparison to control MVECs, PAH MVECs showed increased protein expression of sodium glucose cotransporter 2. Empagliflozin enhanced expression of mitochondrial\u2010encoded genes and respiration, while attenuating oxidative stress and proliferation of PAH MVECs. In SU5416 and hypoxia rats, chronic empagliflozin treatment reduced pulmonary vascular resistance and thickening of the intima of small pulmonary arteries. Finally, 8 patients diagnosed with idiopathic and heritable PAH were enrolled in EMPHOWER PoC. No discontinuation of empagliflozin during the study period or treatment\u2010associated serious adverse events were observed. There were no changes in N\u2010terminal pro\u2010B\u2010type natriuretic peptide, World Health Organization functional class, 6\u2010minute walk distance, or emPHasis score; however, right ventricular ejection fraction slightly worsened (from 45%\u00b110% to 38%\u00b112%,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      =0.031).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Empagliflozin attenuates proliferation of PAH MVECs. Empagliflozin reduces pulmonary vascular remodeling in experimental PAH. While 12\u2009weeks of empagliflozin treatment was feasible in patients with idiopathic or hereditary PAH, we observed signs of right ventricular deterioration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifiers: NCT05493371.\n                    <\/jats:p>\n                  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