Mesenchymal stem cell-derived exosomes improve vascular remodeling by inhibiting EGFR/ErbB2 heterodimerization in hypoxic pulmonary hypertension.

A key characteristic of hypoxic pulmonary hypertension (HPH) is pulmonary vascular remodeling, involving abnormal proliferation and migration of pulmonary artery smooth muscle cells (PASMCs). Recent studies indicate that mesenchymal stem cell-derived exosomes (MSC-exo) exhibit therapeutic effects on HPH. MSC-exosomes were isolated from the conditioned medium of bone mesenchymal stem cells using ultracentrifugation, confirmed via Western blotting (WB), transmission electron microscopy (TEM), and nanoparticle tracking analyses (NTA). Platelet-derived growth factor BB (PDGFBB) induced pathological behavior in PASMCs, replicating the conditions observed in HPH. HPH rats were subjected to a low oxygen environment (10 ± 1% oxygen) for 8 h daily over 28 days. Parameters such as right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and pulmonary vascular remodeling were evaluated. MSC-exosomes suppressed PDGFBB-induced proliferation and migration of PASMCs. Additionally, MSC-exosomes protected rats from hypoxia-induced increases in RVSP, right ventricular hypertrophy, and pulmonary vascular remodeling. The expression of epidermal growth factor receptor (EGFR) and Erb-B2 receptor tyrosine kinase 2 (ErbB2) was investigated in both HPH lung tissues and PDGFBB-induced PASMCs. Results indicated significant upregulation of EGFR/ErbB2 expression in HPH and PDGFBB-induced PASMCs, which was suppressed by MSC-exosomes. The study demonstrates that MSC-exosomes inhibit the development of HPH by suppressing excessive proliferation and migration of PASMCs through the inhibition of EGFR/ErbB2 heterodimerization.