Bench to beside:the imbalance of mutual regulation of homocysteine and hydrogen sulfide in congenital heart disease related pulmonary arterial hypertension  

作　　者：XU Yu-kai SUN Ling JIANG Qiu-ping XIE Yu-Mei WANG Shu-shui ZHANG Zhi-wei 许毓楷;孙凌;蒋秋平;谢育梅;王树水;张智伟(Guangdong Cardiovascular institute,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,Guangdong Province,China;Department of Pediatric Cardiology,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangdong Cardiovascular institute,Guangdong Provincial Key Laboratory of South China Structural Heart Disease)

机构地区：[1]Guangdong Cardiovascular institute,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,Guangdong Province,China [2]Department of Pediatric Cardiology,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangdong Cardiovascular institute,Guangdong Provincial Key Laboratory of South China Structural Heart Disease

出　　处：《South China Journal of Cardiology》2022年第1期39-52,共14页岭南心血管病杂志（英文版）

基　　金：supported by Science and Technology Planning Project of Guangdong Province(No.2018KJY2017)。

摘　　要：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.

关 键 词：Pulmonary arterial hypertension HOMOCYSTEINE hydrogen sulfide pulmonary artery endothelial cells endoplasmic reticulum stress 

分 类 号：R725.4[医药卫生—儿科]