title: H2S inhibits pulmonary arterial endothelial cell inflammation in rats with monocrotaline-induced pulmonary hypertension.
abstract: This study aimed to determine whether hydrogen sulfide (H2S) inhibits pulmonary arterial endothelial inflammation in rats with monocrotaline (MCT)-induced pulmonary hypertension and its possible mechanisms. Twenty-four male Wistar rats were divided randomly into control, MCT, and MCT+H2S treatment groups. Human pulmonary arterial endothelial cells (HPAEC) were cultured and divided into four groups: control, MCT, MCT+H2S, and H2S. Pulmonary artery pressure was determined using a right cardiac catheterization procedure 3 weeks after MCT administration. Pulmonary vascular morphological changes and inflammatory infiltration were measured. Endogenous H2S levels, cystathionine-γ-lyase (CSE) expression, and inflammatory cytokines were determined both in vivo and in vitro. In addition, phosphorylation of NF-κB p65 and IκBα was detected by western blotting, and NF-κB p65 nuclear translocation, as well as its DNA-binding activity, was determined. Pulmonary hypertension and vascular remolding developed 3 wks after MCT administration, with elevated lung tissue inflammatory infiltration and cytokine level associated with activation of the NF-κB pathway, both in vivo and in vitro. However, the endogenous H2S/CSE pathway was downregulated in MCT rats. By contrast, an H2S donor markedly reduced pulmonary artery pressure, pulmonary vascular structural remolding, and increased lung inflammatory infiltration and cytokine levels of MCT-treated rats. Meanwhile, H2S reversed the activation of the NF-κB pathway successfully. The downregulated pulmonary arterial endothelial H2S/CSE pathway is involved in the pulmonary inflammatory response in MCT-treated pulmonary hypertensive rats. H2S attenuated endothelial inflammation by inhibiting the NF-κB pathway.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Feng
authors.affiliation: Department of Cardiac Surgery, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
authors.forename: Siyao
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Da
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Cardiovascular Diseases, Peking University First Hospital, Beijing, China.|Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing, China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism / Q000494:pharmacology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D016686:Monocrotaline; D010766:Phosphorylation / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D017208:Rats, Wistar; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D051996:Transcription Factor RelA; D016686:Monocrotaline; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide