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Research Article
 
DOI:10.11909/j.issn.1671-5411.2019.11.007
Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension
Lin SHI,Xiao-Yun LIU,Zhi-Gang HUANG,Zhi-Yi MA,Yang XI,Lu-Yan WANG,Ning-Ling SUN.Endogenous hydrogen sulfide and ERK1/2 - STAT3 signaling pathway may participate in the association between homocysteine and hypertensionJ Geriatr Cardiol 2019,16(11):822~834
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Authors:Lin SHI1;Xiao-Yun LIU1;Zhi-Gang HUANG2;Zhi-Yi MA3;Yang XI3;Lu-Yan WANG3;Ning-Ling SUN3

Author Affiliation: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;3.Hypertension Research Laboratory, Department of Cardiology, Peking University People’s Hospital, Beijing, China;

Foundation:

Abstract: 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 hyperhomocysteinemia (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 serum Hcy levels and decreased after folate treatment. Angiotensin converting enzyme 1 (ACE1) expression in the Wistar Hcy group was enhanced comparing to controls, but was decreased in the Wistar folate group. Angiotensin II receptor type 1 (AGTR1) levels in the kidney tissue increased in the Wistar folate group. Both serum H2S and kidney cystathionine γ-lyase decreased with elevated levels of serum Hcy. In vitro, increased concentrations and treatment 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 mediate 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.

Keywords:

Angiotensin converting enzyme 1; Blood pressure; ERK1/2-STAT3 signaling pathway; Homocysteine; Hydrogen sulfide
Received:May 28, 2019        Accepted:October 23, 2019   Published Online:November 28, 2019
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