Protective effect of hydrogen sulfide on monocrotaline‑induced pulmonary arterial hypertension via inhibition of the endothelial mesenchymal transition

Endothelial-to-mesenchymal transition (EndMT) serves an important role in the vascular remodeling of pulmonary arterial hypertension (PAH). However, little is known about the correlation between hydrogen sulfide (H2 S), a protective gaseous mediator in PAH and the process of EndMT. Male Sprague-dawley rats (10 weeks old) received a single dose of monocrotaline (McT; i.p., 60 mg/kg) and were randomly treated with NaHS [an H2 S donor; intraperitoneal (i.p.) 1 mg/kg/day], dL-propagylglycine (an inhibitor of H2 S synthesis; PAG; i.p., 10 mg/kg/day) or saline, 7 days after McT injection. Rats were sacrificed 21 days after MCT injection. A selection of human pulmonary artery endothelial cells (HPAEcs) were pretreated with NaHS or saline and stimu- lated with transforming growth factor (TGF)-β1 (10 ng/ml), and the other HPAEcs were transfected with a cystathionine γ-lyase (cSE, an H2 S synthesizing enzyme) plasmid and subsequently stimulated with TGF-β1. NaHS was indicated to inhibit EndMT and PAH progression by inhibiting the induc- tion of the nuclear factor (NF)-κB-Snail pathway. In contrast, the depletion of H2 S formation by PAG exacerbated EndMT and PAH by activating NF-κB-Snail molecules. In HPAEcs, NaHS dose-dependently inhibited TGF-β1-induced EndMT and the activation of the NF-κB-Snail pathway. Transfection with a CSE plasmid significantly repressed TGF‑β1-induced expression of the mesenchymal marker and upregulated the expression of the endothelial marker, which was accompanied by the suppression of the NF-κB-Snail pathway. The inhibi- tory effect of cSE overexpression on TGF-β1-induced EndMT was significantly reversed by pretreatment with PAG. In conclusion, the current study provides novel information eluci- dating the beneficial effect of H2 S on PAH through inhibiting the induction of the NF-κB-Snail pathway and the subsequent process of EndMT in pulmonary arteries.