{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:40Z","timestamp":1787028580480,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T00:00:00Z","timestamp":1771113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["GMR25133328"],"award-info":[{"award-number":["GMR25133328"]}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"crossref","award":["P30ES030283"],"award-info":[{"award-number":["P30ES030283"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000066","name":"NIEHS","doi-asserted-by":"crossref","award":["T32ES011564"],"award-info":[{"award-number":["T32ES011564"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"crossref","award":["U18TR003787"],"award-info":[{"award-number":["U18TR003787"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Our previous studies have shown that continuous infusion of angiotensin II (Ang II) in C57BL\/6J mice causes dysfunction and a cachexia-like pathogenesis in both skeletal muscle and the left ventricle, which is significantly reduced by withaferin A (WFA), a steroidal lactone. However, it remains unknown whether WFA can reverse right ventricular (RV) dysfunction induced by Ang II. To determine the effects of WFA in attenuating Ang II-induced RV dysfunction, we employed a model in which continuous Ang II infusion via an osmotic pump in C57BL\/6J mice induced cardiac remodeling. We then focused on investigating RV performance and structural changes using echocardiography and histopathological examination, as well as quantitative real-time PCR (qRT-PCR) for mRNA expression. Echocardiographic analysis demonstrated that Ang II significantly increased RV wall thickness and impaired RV systolic and diastolic function, as indicated by reductions in tricuspid annular plane systolic excursion, TV E\/E\u2032 ratio, RV S\u2032, and RVOT VTI. The qRT-PCR analysis revealed marked upregulation of pro-fibrotic markers, including TGF-\u03b2, fibronectin, and collagen. WFA treatment restored RV functions and significantly attenuated Ang II-induced RV dysfunction and fibrosis. Our findings provide the first evidence that WFA attenuates Ang II-induced cachexia-like remodeling and dysfunction of the RV. These results position WFA as a compelling therapeutic candidate for cardiac cachexia, offering direct anti-fibrotic and cardioprotective benefits that warrant further translational development.<\/jats:p>","DOI":"10.3390\/ijms27041877","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T10:14:32Z","timestamp":1771236872000},"page":"1877","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Withaferin A Attenuates Angiotensin II-Induced Right Ventricular Dysfunction and Fibrosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1815-0317","authenticated-orcid":false,"given":"Darini","family":"Nagarajan","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasa","family":"Vemuri","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Kratholm","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dakotah","family":"Cathey","sequence":"additional","affiliation":[{"name":"Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranjal","family":"Sharma","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3048-1135","authenticated-orcid":false,"given":"Lu","family":"Cai","sequence":"additional","affiliation":[{"name":"Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"},{"name":"Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-8400","authenticated-orcid":false,"given":"Jiapeng","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA"},{"name":"Center for Integrative Environmental Health Sciences, University of Louisville, Louisville, KY 40202, USA"},{"name":"Department of Anesthesiology and Perioperative Medicine, University of Louisville, Louisville, KY 40202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0071-0198","authenticated-orcid":false,"given":"Mariusz Z.","family":"Ratajczak","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, KY 40202, USA"},{"name":"Brown Cancer Center, University of Louisville, Louisville, KY 40220, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2415-3314","authenticated-orcid":false,"given":"Mahavir","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville, Louisville, KY 40202, USA"},{"name":"Brown Cancer Center, University of Louisville, Louisville, KY 40220, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sham S.","family":"Kakar","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Louisville, Louisville, KY 40202, USA"},{"name":"Brown Cancer Center, University of Louisville, Louisville, KY 40220, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kakar, S.S., Vemuri, V., and Ratajczak, M.Z. 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