Mesenchymal Stem Cell-based Apelin Gene Therapy Improves Pulmonary Artery Remodeling in Monocrotaline-induced Pulmonary Hypertension Through PI3K/AKT/eNOS and ERK1/2 Signaling Pathways.

Abstract

Pulmonary arterial hypertension (PAH) poses a challenge due to limited curative options and ineffective treatments. Mesenchymal stem cell (MSC) therapy has emerged as a potential intervention for PAH. This study delved into the therapeutic potential and molecular mechanisms underlying MSC-based apelin gene therapy in PAH rats induced by monocrotaline (MCT). Wharton's jelly-derived MSCs transfected with pcSLenti-APLN were utilized as therapeutic agents. Transplanted MSCs successfully homed to the lung tissue of rats and sustained survival for at least three weeks. MSC-mediated apelin gene therapy effectively reduced pulmonary artery pressure, mitigated pulmonary vascular remodeling, and modulated apoptosis in MCT-induced PAH rats. Furthermore, the phosphatidylinositol 3-kinase (PI3K)/AKT/endothelial nitric oxide synthase (eNOS) and ERK1/2 signaling pathways were involved in the therapeutic effects. Meanwhile, Apelin-MSCs also regulated MCT-induced changes of Bax and Bcl-2 in the lung lobes and pulmonary arterioles. MSC-based apelin gene therapy could be considered a possible therapeutic strategy for PAH.