Background To determine the imbalance of mutual regulation of homocysteine and hydrogen sulfide(H;S)in congenital heart disease(CHD)-related pulmonary arterial hypertension(PAH)among pediatric patients,and explore pos...Background To determine the imbalance of mutual regulation of homocysteine and hydrogen sulfide(H;S)in congenital heart disease(CHD)-related pulmonary arterial hypertension(PAH)among pediatric patients,and explore possible mechanisms.Methodology and Principal Findings:In this study,we regulated homocysteine concentrations to observe the relations between homocysteine and H;S.Cell viability and activity of metabolic enzymes were determined.Cytological experiments demonstrated that exogenous or endogenous H;S both had protective 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 homocysteine and H;S were in a dynamic change,which was related to the homocysteine concentration.When the homocysteine concentrations were low(≤30μmol/L),the protective effects of H;S can resist the homocysteine-induced damage 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 H;S and the OD values of cystathionine gamma-lyase(CSE)were lower in the PAH group.All the CHD-PAH patients had low homocysteine(≤30μmol/L)concentrations still lead to PAH because of decreased the protective effects of H;S due to the decreased activity of CSE.Conclusion:Homocysteine and H;S both take part in the development of CHD-PAH.Hyperhomocysteinemia may be the pathogenic factor,while H;S is the protective factor.The mutual dynamic regulations are related to the homocysteine concentration.The clinical trials and cytological experiment results have great implications for clinical practice.For patients with PAH,not only the damage of homocysteine to endothelial cells,but also we should pay attention to the decreased protection of H;S and activity of metabolic enzymes.展开更多
基金supported by Science and Technology Planning Project of Guangdong Province(No.2018KJY2017)。
文摘Background To determine the imbalance of mutual regulation of homocysteine and hydrogen sulfide(H;S)in congenital heart disease(CHD)-related pulmonary arterial hypertension(PAH)among pediatric patients,and explore possible mechanisms.Methodology and Principal Findings:In this study,we regulated homocysteine concentrations to observe the relations between homocysteine and H;S.Cell viability and activity of metabolic enzymes were determined.Cytological experiments demonstrated that exogenous or endogenous H;S both had protective 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 homocysteine and H;S were in a dynamic change,which was related to the homocysteine concentration.When the homocysteine concentrations were low(≤30μmol/L),the protective effects of H;S can resist the homocysteine-induced damage 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 H;S and the OD values of cystathionine gamma-lyase(CSE)were lower in the PAH group.All the CHD-PAH patients had low homocysteine(≤30μmol/L)concentrations still lead to PAH because of decreased the protective effects of H;S due to the decreased activity of CSE.Conclusion:Homocysteine and H;S both take part in the development of CHD-PAH.Hyperhomocysteinemia may be the pathogenic factor,while H;S is the protective factor.The mutual dynamic regulations are related to the homocysteine concentration.The clinical trials and cytological experiment results have great implications for clinical practice.For patients with PAH,not only the damage of homocysteine to endothelial cells,but also we should pay attention to the decreased protection of H;S and activity of metabolic enzymes.
