{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T19:17:07Z","timestamp":1777576627232,"version":"3.51.4"},"reference-count":33,"publisher":"SAGE Publications","issue":"4-5","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL128831"],"award-info":[{"award-number":["R01HL128831"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL46716"],"award-info":[{"award-number":["R01HL46716"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["T32HL160517"],"award-info":[{"award-number":["T32HL160517"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006418","name":"Brown University","doi-asserted-by":"publisher","award":["Armond Versaci Research Fellowship"],"award-info":[{"award-number":["Armond Versaci Research Fellowship"]}],"id":[{"id":"10.13039\/100006418","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Asian Cardiovasc Thorac Ann"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Left heart failure is the most common cause of pulmonary hypertension and increases morbidity and mortality. We investigate the use of canagliflozin, an antidiabetic Sodium-glucose Cotransporter-2 Inhibitor, which is first-line therapy in congestive heart failure, on pulmonary fibrosis in a porcine model of chronic myocardial ischemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Sixteen Yorkshire swine, eight in a normal diet control arm (NDC) and eight in the canagliflozin arm (CAN), underwent left thoracotomy and ameroid constrictor placement on the left circumflex artery. Seven weeks after placement, the swine underwent harvest procedure. During harvest, left ventricular contractility was quantified by direct left ventricular pressure-volume loops. Protein expression was quantified by immunoblotting and Masson's trichrome staining was utilized to assess perivascular collagen deposition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Analysis of left ventricular ejection fraction demonstrated no significant difference between CAN and NDC. Western blot analysis demonstrated increases in TGF\u03b2 signaling pathways with decreased free TGF\u03b2 and TGF\u03b2 monomers in CAN pigs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Downstream mediators of TGF\u03b2 were also increased in NDC with an increase in phospho-SMAD2\/3 activity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005). Masson's Trichrome analysis of lung tissue demonstrated a trend toward reduced perivascular collagen deposition in CAN swine lungs (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.086).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Canagliflozin ameliorates chronic fibrotic changes related to pulmonary hypertension in left ventricular failure. While there was a strong trend toward significance in histologic analysis, this may be limited by the duration of our model. Western blot analysis, however, demonstrates that CAN's modulation of TGF\u03b2 signaling pathways may play a role in the management of secondary pulmonary hypertension.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02184923251352222","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T04:12:48Z","timestamp":1751515968000},"page":"188-195","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Canagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces lung fibrosis in left heart dysfunction"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7581-0555","authenticated-orcid":false,"given":"Meghamsh","family":"Kanuparthy","sequence":"first","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwight D","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Broadwin","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher","family":"Stone","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jad","family":"Hamze","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5974-8692","authenticated-orcid":false,"given":"Keertana","family":"Yalamanchili","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharif","family":"Sabe","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank W","family":"Sellke","sequence":"additional","affiliation":[{"name":"Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202104200"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200510-1668OC"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2015.01.030"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.12-1752"},{"key":"e_1_3_2_6_2","volume-title":"Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors","author":"Padda IS","year":"2023","unstructured":"Padda IS, Mahtani AU, Parmar M. Sodium-Glucose Transport Protein 2 (SGLT2) Inhibitors. Treasure Island (FL): StatPearls Publishing, 2023."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206286"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1911303"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2030183"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01429-5"},{"key":"e_1_3_2_12_2","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on clinical practice guidelines","volume":"79","author":"Heidenreich PA","year":"2022","unstructured":"Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA\/ACC\/HFSA guideline for the management of heart failure: a report of the American College of Cardiology\/American Heart Association Joint Committee on clinical practice guidelines. Circulation 2022; 79: e263\u2013e421.","journal-title":"Circulation"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2024.1914"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00167.2015"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.01.015"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-022-01939-7"},{"key":"e_1_3_2_17_2","first-page":"1045","article-title":"Proteomic analysis and sex-specific changes in chronically ischemic swine myocardium treated with sodium-glucose cotransporter-2 inhibitor canagliflozin","volume":"10","author":"Harris DD","year":"2023","unstructured":"Harris DD, Sabe SA, Broadwin M, et al. Proteomic analysis and sex-specific changes in chronically ischemic swine myocardium treated with sodium-glucose cotransporter-2 inhibitor canagliflozin. J Am Coll Surg 2023; 238; 10: 1045\u20131055.","journal-title":"J Am Coll Surg"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surg.2023.09.043"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmccpl.2023.100052"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12030588"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2024.06.004"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/mps7010017"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-17204-5"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.hfc.2008.11.008"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2011.059881"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1101\/2022.11.28.22282821"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12968-016-0283-9"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200707-1083OC"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.4402"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1503184"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209655"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201908-1640OC"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23420-4"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-014-1619-7"}],"container-title":["Asian Cardiovascular and Thoracic Annals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02184923251352222","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/02184923251352222","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/02184923251352222","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:28:56Z","timestamp":1777404536000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/02184923251352222"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":33,"journal-issue":{"issue":"4-5","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1177\/02184923251352222"],"URL":"https:\/\/doi.org\/10.1177\/02184923251352222","relation":{},"ISSN":["0218-4923","1816-5370"],"issn-type":[{"value":"0218-4923","type":"print"},{"value":"1816-5370","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6]]}}}