Amonafide Targeting NTSR1-PI3K/AKT/mTOR Signaling Attenuates Vascular Remodeling in Pulmonary Arterial Hypertension - PubMed
3 hours ago
- #Pulmonary Arterial Hypertension
- #Vascular Remodeling
- #Amonafide
- Topoisomerase II α is upregulated in idiopathic PAH, rodent PAH models, and PDGF-BB-stimulated pulmonary artery smooth muscle cells, linked to increased DNA damage and apoptosis resistance.
- Amonafide, a topoisomerase II inhibitor, improves hemodynamics, reduces right ventricular hypertrophy, and suppresses vascular remodeling in animal models, while inhibiting proliferation, migration, apoptosis resistance, and DNA damage in cells.
- Mechanistically, amonafide downregulates NTSR1 expression and inhibits the PI3K/AKT/mTOR signaling pathway, with NTSR1 overexpression abolishing and NTSR1 knockdown enhancing its effects.
- The study suggests targeting topoisomerase II α and NTSR1 as a promising therapeutic approach for PAH.