{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T17:43:23Z","timestamp":1791999803541,"version":"4.4.0"},"reference-count":54,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Uniformed Services University of the Health Sciences Intramural Early Career Scientist Award","award":["R089354417"],"award-info":[{"award-number":["R089354417"]}]},{"name":"Uniformed Services University of the Health Sciences Intramural Early Career Scientist Award","award":["HU00012120008"],"award-info":[{"award-number":["HU00012120008"]}]},{"name":"Defense Health Agency","award":["R089354417"],"award-info":[{"award-number":["R089354417"]}]},{"name":"Defense Health Agency","award":["HU00012120008"],"award-info":[{"award-number":["HU00012120008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Loop diuretics like furosemide are commonly used in heart failure (HF) treatment, but their effects on disease progression are still unclear. Furosemide treatment accelerates HF deterioration in a swine model, but the mechanism of acceleration is poorly understood. We hypothesized that furosemide activates inflammatory signaling in the failing left ventricular (LV) myocardium, leading to adverse remodeling of the extracellular matrix (ECM). A total of 14 Yorkshire pigs underwent permanent transvenous pacemaker implantation and were paced at 200 beats per minute; 9 non-instrumented pigs provided controls. Seven paced animals received normal saline, and seven received furosemide at a dose of 1 mg\/kg intramuscularly. Weekly echocardiograms were performed. Furosemide-treated animals reached the HF endpoint a mean of 3.2 days sooner than saline-treated controls (mean 28.9 \u00b1 3.8 SEM for furosemide and 32.1 \u00b1 2.5 SEM for saline). The inflammatory signaling protein transforming growth factor-beta (TGF-\u03b2) and its downstream proteins were significantly (p \u2264 0.05) elevated in the LV after furosemide treatment. The regulatory factors in cell proliferation, mitogen-activated protein kinase signaling pathway proteins, and matrix metalloproteinases were elevated in the furosemide-treated animals (p \u2264 0.05). Our data showed that furosemide treatment increased ECM remodeling and myocardial fibrosis, reflecting increased TGF-\u03b2 signaling factors, supporting prior results showing worsened HF.<\/jats:p>","DOI":"10.3390\/ijms26136088","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T05:53:13Z","timestamp":1750917193000},"page":"6088","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Furosemide Promotes Inflammatory Activation and Myocardial Fibrosis in Swine with Tachycardia-Induced Heart Failure"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1251-3497","authenticated-orcid":false,"given":"Nisha","family":"Plavelil","sequence":"first","affiliation":[{"name":"Department of Radiology and Bioengineering, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Goldstein","sequence":"additional","affiliation":[{"name":"Department of Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1521-6915","authenticated-orcid":false,"given":"Michael G.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9651-3737","authenticated-orcid":false,"given":"Luke","family":"Michaelson","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Haigney","sequence":"additional","affiliation":[{"name":"Department of Medicine, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6111-9262","authenticated-orcid":false,"given":"Maureen N.","family":"Hood","sequence":"additional","affiliation":[{"name":"Department of Radiology and Bioengineering, F. Edward H\u00e9bert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17308","DOI":"10.1074\/jbc.M112.356014","article-title":"Loop diuretic and ion-binding residues revealed by scanning mutagenesis of transmembrane helix 3 (TM3) of Na-K-Cl cotransporter (NKCC1)","volume":"287","author":"Somasekharan","year":"2012","journal-title":"J. Biol. 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