Brief Article
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World J Gastroenterol. Jan 28, 2014; 20(4): 1079-1087
Published online Jan 28, 2014. doi: 10.3748/wjg.v20.i4.1079
Role of hydrogen sulfide in portal hypertension and esophagogastric junction vascular disease
Chao Wang, Juan Han, Liang Xiao, Chang-E Jin, Dong-Jian Li, Zhen Yang
Chao Wang, Dong-Jian Li, Zhen Yang, Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Juan Han, Department of Biliary and Pancreatic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Liang Xiao, Department of Surgery and Biological Therapy, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong Province, China
Chang-E Jin, Department of Respiratory Medicine, Shenzhen People’s Hospital, Shenzhen 518020, Guangdong Province, China
Author contributions: Wang C, Han J and Xiao L designed the research; Wang C, Han J, Xiao L, Jin CE, Li DJ and Yang Z performed the research; Wang C, Han J, Xiao L and Jin CE analyzed the data; Wang C, Han J and Xiao L wrote the paper.
Supported by Specialized Research Fund for the Doctoral Program of Higher Education of China, No. 20120142120048; and Natural Science Foundation of Hubei Province, China, No. 2012FFB02308
Correspondence to: Chao Wang, PhD, Department of General Surgery, Tongji Hospital, Tongji Medical College, Science and Technology of Huazhong University, No. 1095, Jiefang Avenue, Wuhan 430030, Hubei Province, China. wangchao75@sina.com
Telephone: +86-27-83663008 Fax: +86-27-83663039
Received: August 16, 2013
Revised: October 14, 2013
Accepted: November 18, 2013
Published online: January 28, 2014
Abstract

AIM: To investigate the association between endogenous hydrogen sulfide (H2S) and portal hypertension as well as its effect on vascular smooth muscle cells.

METHODS: Portal hypertension patients were categorized by Child-Pugh score based on bilirubin and albumin levels, prothrombin time, ascites and hepatic encephalopathy. Plasma H2S concentrations and portal vein diameters (PVDs) were compared between portal hypertension patients and control participants, as well as between portal hypertension patients with varying degrees of severity. In addition, we established a rabbit hepatic schistosomiasis portal hypertension (SPH) model and analyzed liver morphology, fibrosis grade, plasma and liver tissue H2S concentrations, as well as cystathionine γ-lyase (CSE) activity and phosphorylated extracellular signal-regulated kinase (pERK)1/2, B cell lymphoma (Bcl)-2 and Bcl-XL expression in portal vein smooth muscle cells, in addition to their H2S-induced apoptosis rates.

RESULTS: In portal hypertension patients, endogenous H2S levels were significantly lower than those in healthy controls. The more severe the disease was, the lower were the H2S plasma levels, which were inversely correlated with PVD and Child-Pugh score. Liver tissue H2S concentrations and CSE expression were significantly lower in the SPH rabbit livers compared with the control animals, starting at 3 wk, whereas pERK 1/2 expressions gradually increased 12-20 wk after SPH model establishment. In portal vein smooth muscle cells, increasing H2S levels led to increased apoptosis, while Bcl-2 and Bcl-XL expression decreased.

CONCLUSION: H2S prevents vascular restructuring caused by excessive proliferation of smooth muscle cells via apoptosis induction, which helps to maintain normal vascular structures.

Keywords: Portal hypertension, Apoptosis, B-cell lymphoma-2, B-cell lymphoma-XL, Cystathionine γ-lyase, pERK 1/2, Hydrogen sulfide

Core tip: In portal hypertension patients, endogenous hydrogen sulfide (H2S) levels were significantly lower than those in healthy controls. H2S plasma level reductions correlated with portal vein diameter and Child-Pugh score. In a rabbit hepatic schistosomiasis portal hypertension model, liver tissue H2S concentrations and cystathionine γ-lyase expression were significantly reduced and phosphorylated extracellular signal regulated kinase 1/2 expression gradually increased. Increasing H2S levels led to increased apoptosis of portal vein smooth muscle cells, while B-cell lymphoma-2 (Bcl-2) and Bcl-XL expression decreased. We suggest that H2S prevents portal hypertension though apoptosis induction of otherwise excessive proliferating smooth muscle cells.