摘要Background To determine the imbalance of mutual regulation of homocysteine and hydrogen sulfide(H2S)in congenital heart disease(CHD)-related pulmonary arterial hypertension(PAH)among pediatric patients,and ex-plore possible mechanisms.Methodology and Principal Findings:In this study,we regulated homocysteine con-centrations to observe the relations between homocysteine and H2S.Cell viability and activity of metabolic en-zymes were determined.Cytological experiments demonstrated that exogenous or endogenous H2S both had protec-tive effects on HPAECs and can inhibit homocysteine-induced apoptosis.The possible mechanisms were correlated with GRP78 and CHOP expressions of endoplasmic reticulum stress pathway.In addtion,we found that homocyste-ine and H2S were in a dynamic change,which was related to the homocysteine concentration.When the homocyste-ine concentrations were low(≤30 μmol/L),the protective effects of H2S can resist the homocysteine-induced dam-age effects.However,the cytological results were different from the clinical data.Our clinical study had showed that the levels of homocysteine were higher,the levels of H2S and the OD values of cystathionine gamma-lyase(CSE)were lower in the PAH group.All the CHD-PAH patients had low homocysteine(≤30 μmol/L)concentra-tions still lead to PAH because of decreased the protective effects of H2S due to the decreased activity of CSE.Con-clusion:Homocysteine and H2S both take part in the development of CHD-PAH.Hyperhomocysteinemia may be the pathogenic factor,while H2S is the protective factor.The mutual dynamic regulations are related to the homocys-teine concentration.The clinical trials and cytological experiment results have great implications for clinical prac-tice.For patients with PAH,not only the damage of homocysteine to endothelial cells,but also we should pay at-tention to the decreased protection of H2S and activity of metabolic enzymes.