β-Alanine supplementation ameliorates right ventricular remodeling caused by MCT-induced pulmonary hypertension

Background Pulmonary hypertension (PH) is a disease characterized by progressive pulmonary vascular resistance and right heart failure. Beta-alanine (β-Ala), a non-proteinogenic amino acid, exhibits potential cardiovascular benefits; however, its role in PH pathophysiology remains underexplored. Objective To assess the effects of β-Ala supplementation on right ventricular remodeling and dysfunction in a monocrotaline (MCT)-induced PH rat model. Methods Male Wistar rats were randomly divided into three groups: control, MCT-induced PH, and β-Ala treated PH. Right ventricular function was evaluated using RVSP and RVHI. Protein expression and mRNA levels of cardiac markers and signaling pathways were analyzed by Western blotting and qPCR. Histological analysis was performed to assess right ventricular hypertrophy and fibrosis. Results β-Ala supplementation significantly improved RVSP and RVHI in MCT-induced PH rats. Protein expression analysis showed reduced ERK and p38 MAPK, along with increased activation of AKT in the β-Ala group compared to the MCT group. Additionally, β-Ala reduced the expression of pro-apoptotic markers Bax and Caspase-3 while increasing levels of the anti-apoptotic protein Bcl-2. qPCR analysis revealed decreased expression of ANP, BNP, α-MHC, β-MHC, and TGF-β in the β-Ala group. Histological analysis confirmed that β-Ala treatment alleviated right ventricular hypertrophy and fibrosis. Conclusion β-Ala improves right ventricular remodeling and dysfunction in MCT-induced PH rats by modulating signaling pathways and apoptotic markers, indicating its potential as a therapeutic agent for PH-induced right heart dysfunction.