Work

Effect of betaine on pulmonary arterial hypertension treatment and mechanisms based on the PERK-eIF2α signal-pathway

Year: 2025

Type: article

Abstract: PAH is marked by excessive PASMCs and resistance to apoptosis. ERS drives pulmonary vascular remodeling. Betaine from Lycium barbarum L. protects against PAH, is orally available to humans and shows no obvious toxicity for humans and animals at 100, 200, 400 mg/kg. However, the ERS link remains unexplored. This study investigates betaine's PAH protective mechanisms. SD rats received a single subcutaneous injection of notaline to induce PAH and received betaine and sildenafil avenate for 21 d. Betaine significantly improved abnormal changes in echocardiography, hemodynamics, and pathomorphology. Betaine inhibited the proliferation of HPASMCs induced by PDGF-BB. Moreover, betaine suppressed the protein expression of GRP78 and improved the protein expression of p-PERK in rat lungs. It also significantly upregulated PERK and eIF2α phosphorylation in HPASMCs. Upon PERK siRNA knockdown, betaine restores PERK and eIF2α phosphorylation. Betaine activates PERK-eIF2α, mitigates ERS, and targets PERK, as a potential PAH therapy. • This study explored betaine's impacts and mechanisms in treating PAH. • Betaine improved echocardiographic and hemodynamic indices in PAH rat models, delayed right ventricular hypertrophy, and reversed vascular remodeling induced by MCT. • Betaine also inhibited PDGF-BB-stimulated HPASMC proliferation in vitro. • Betaine, shown to alleviate PAH and curb PDGF-BB-induced HPASMC proliferation, activated the PERK-eIF2α pathway, reduced ER stress, and reversed pulmonary vascular remodeling, suggesting its potential as a PAH-treatment target.

Source: Journal of Functional Foods

DOI: 10.1016/j.jff.2025.106780