Therapeutic effects of fingolimod through sphingosine-1-phosphate signaling in pulmonary arterial hypertension - PubMed
4 days ago
- #Pulmonary arterial hypertension
- #Fingolimod
- #Sphingosine-1-phosphate signaling
- Fingolimod, an immunosuppressive drug, shows therapeutic effects in pulmonary arterial hypertension (PAH) by modulating sphingosine-1-phosphate (S1P) signaling.
- PAH is characterized by pulmonary vascular remodeling due to abnormal proliferation of pulmonary arterial smooth muscle cells (PASMCs) and perivascular inflammatory macrophages.
- Fingolimod inhibits abnormal proliferation of idiopathic PAH-PASMCs (IC50 = 3.8 μM) and reduces viability of CD163-positive macrophages.
- S1P receptor 3, predominantly expressed in PASMCs, is upregulated in IPAH-PASMCs and MCT-PAH rats.
- Fingolimod administration (1 mg/kg/day) decreases perivascular macrophage accumulation, lowers right ventricular systolic pressure, and attenuates pulmonary vascular remodeling in MCT-PAH rats.
- Fingolimod improves survival in experimental PAH rats, suggesting its potential as a repositioning strategy for PAH therapy.