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

Area of Science:

• Cardiovascular Research
• Pharmacology
• Molecular Biology

Background:

• Angiotensin II (Ang II) infusion causes cardiac dysfunction and cachexia in mice.
• Previous studies showed Withaferin A (WFA) reduces left ventricular dysfunction.
• The effect of WFA on Ang II-induced right ventricular (RV) dysfunction is unknown.

Purpose of the Study:

• To investigate the therapeutic potential of WFA in attenuating Ang II-induced RV dysfunction and remodeling.
• To determine if WFA can reverse RV cachexia-like pathogenesis.

Main Methods:

• Ang II infusion in C57BL/6J mice to induce RV dysfunction.
• Echocardiography to assess RV performance and structure.
• Histopathological examination and qRT-PCR for fibrosis markers.

Main Results:

• Ang II increased RV wall thickness and impaired systolic/diastolic function.
• Ang II upregulated pro-fibrotic markers (TGF-β, fibronectin, collagen).
• WFA treatment restored RV function and attenuated fibrosis.

Conclusions:

• WFA attenuates Ang II-induced RV cachexia-like remodeling and dysfunction.
• WFA demonstrates anti-fibrotic and cardioprotective effects on the RV.
• WFA is a potential therapeutic candidate for cardiac cachexia.