What question did this study set out to answer?

This research investigates whether withaferin A can reverse right ventricular dysfunction caused by angiotensin II.

February 17, 2026Open Access

Withaferin a Attenuates Angiotensin II-Induced Right Ventricular Dysfunction and Fibrosis

Q: What does this research mean for the field?

Withaferin A significantly restores right ventricular function and reduces fibrosis induced by angiotensin II in mice, reversing RV dysfunction. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Withaferin A significantly restored right ventricular function and reduced fibrosis induced by angiotensin II in mice, reversing RV dysfunction.

Key Points

This research investigates whether withaferin A can reverse right ventricular dysfunction caused by angiotensin II.
Utilized C57BL/6J mice with continuous angiotensin II infusion via an osmotic pump.
Conducted echocardiographic assessments to evaluate right ventricular function.
Performed histopathological examination of cardiac tissue.
Employed quantitative real-time PCR (qRT-PCR) to assess mRNA expression of fibrotic markers.
Angiotensin II infusion increased right ventricular wall thickness and impaired systolic and diastolic function.
Withaferin A treatment restored right ventricular functions and reduced angiotensin II-induced fibrosis.
Pro-fibrotic markers like TGF-β, fibronectin, and collagen were significantly upregulated due to angiotensin II but were attenuated with withaferin A.

Structured PICO

Does withaferin A attenuate right ventricular dysfunction and fibrosis in a mouse model of Ang II-induced cardiac remodeling?

Population

C57BL/6J mice with continuous angiotensin II (Ang II) infusion via osmotic pump inducing cardiac remodeling

Intervention

Withaferin A (WFA)

Comparator

Ang II infusion alone (implied)

Outcome

Right ventricular performance and structural changes measured by echocardiography and histopathologysurrogate

Withaferin A attenuates Ang II-induced right ventricular dysfunction and fibrosis in mice, suggesting potential as a therapeutic candidate for cardiac cachexia.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

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 instigating 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′ ratio, RV S′, and RVOT VTI. The qRT-PCR analysis revealed marked upregulation of pro-fibrotic markers, including TGF-β, 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.