Endogenous hydrogen sulfide and ERK1/2-STAT3signaling pathway may participate in the association between homocysteine and hypertension
Lin SHI1
Xiao-Yun LIU1
Zhi-Gang HUANG2
Zhi-Yi MA1
Yang XI1
Lu-Yan WANG1
Ning-Ling SUN1
1.Hypertension Research Laboratory,Department of Cardiology,Peking University People 's Hospital,Beijing,China 2.Hypertension Research Laboratory,Department of Cardiology,Peking University People 's Hospital,Beijing,China;Emergency Department,Peking University Shenzhen Hospital,Shenzhen,China
摘要：Background Homocysteine(Hcy)is a risk factor for hypertension,although the mechanisms are poorly understood.Methods We first explored the relationship between Hcy levels and blood pressure(BP)by analyzing the clinical data of primary hypertensive patients admitted to our hospital.Secondly,we explored a rat model to study the effect of Hcy on blood pressure and the role of H2S.An hyperho-mocysteinemia(HHcy)rat model was induced to explore the effect of Hcy on blood pressure and the possible mechanism.We carried out tissue histology,extraction and examination of RNA and protein.Finally,we conducted cell experiments to determine a likely mechanism through renin-angiotensin-aldosterone system(RAAS)and extracellular signal-regulated kinase 1/2(ERK1/2)signaling pathway.Results In primary hypertensive inpatients with HHcy,blood pressure was significantly higher as compared with inpatient counterparts lacking HHcy.In the rat model,blood pressure of the Wistar rats was significantly increased with increases in serurn Hcy levels and decreased after folate treatrnent.Angiotensin converting enzyme 1(ACE1)expression in the Wistar Hcy group was enhanced comparing to controls,but was de-creased in the Wistar folate group.Angiotensin Ⅱ receptor type 1(AGTR1)levels in the kidney tissue increased in the Wistar folate group.Both serurn H2S and kidney cystathionine γ-lyase decreased with elevated levels of serum Hcy.In vitro,increased concentrations and treat-ment times for Hcy were associated with increased expression of collagen type 1 and AGTR1.This dose and time dependent response was also observed for p-STAT3 and p-ERK1/2 expression.Conclusion Endogenous H2S might medlate the process of altered blood pressure in response to changes in serum Hcy levels,in a process that is partly dependent on activated RAAS and ERK1/2-STAT3 signaling pathway.
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论文发表日期：2019-11-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：13( 822-834 )
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