PMID- 28579512
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20180808
IS  - 1095-9319 (Electronic)
IS  - 0026-2862 (Linking)
VI  - 114
DP  - 2017 Nov
TI  - Homocysteine up-regulates endothelin type A receptor in vascular smooth muscle 
      cells through Sirt1/ERK1/2 signaling pathway.
PG  - 34-40
LID - S0026-2862(16)30181-9 [pii]
LID - 10.1016/j.mvr.2017.05.010 [doi]
AB  - Sirtuin 1 (Sirt1) is a longevity gene that has protective effects in 
      cardiovascular diseases (CVDs). The endothelin type A (ET(A)) receptor is 
      involved in pathogenesis of CVDs. The extracellular signal related kinases 1 and 
      2 (ERK1/2) signaling pathway is involved in regulation of the ET(A) receptor 
      induced by some CVD risk factors in vascular smooth muscle cells (VSMCs). 
      Hyperhomocysteinemia (HHcy) is an independent risk factor for CVDs. The present 
      study was designed to investigate the hypothesis that homocysteine up-regulates 
      ET(A) receptor through the Sirt1/ERK1/2 signaling pathway. In vitro experiments 
      were performed in the rat superior mesenteric artery. The rat superior mesenteric 
      artery was cultured with or without homocysteine (Hcy) in the presence and 
      absence of Resveratrol (Res, a Sirt1 agonist), SRT1720 (a specific Sirt1 agonist) 
      or U0126 (an ERK1/2 signaling pathway inhibitor) in serum-free medium for 24h. In 
      vivo, the rats received subcutaneous injections of Hcy in the presence of or 
      absence of Res or U0126 for 3weeks. The contractile response to ET-1 was studied 
      using a sensitive myograph. In addition, the level of protein expression was 
      determined using western blotting. Hcy significantly increased the expression of 
      ET(A) receptor and also increased the ET(A) receptor-mediated contractile 
      response induced by ET-1 in vitro. These effects were inhibited by Res, SRT1720 
      and U0126 treatment. In addition, Hcy down-regulated the level of Sirt1, and 
      up-regulated the level of phosphorylated ERK1/2, which was reversed upon Res or 
      SRT1720 treatment. In vivo results showed that HHcy results in the up-regulation 
      of ET(A) receptor expression, and elevated blood pressure in rats. However, Res 
      and U0126 could block these effects, respectively. In conclusion, these results 
      suggest that Hcy regulates ET(A) receptor expression via the Sirt1/ERK1/2 
      signaling pathway in VSMCs.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Chen, Yulong
AU  - Chen Y
AD  - Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and 
      Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China; 
      Shaanxi Pharmaceutical Development Center, Shaanxi Pharmaceutical Holding Group 
      Co., Ltd., Xi'an, Shaanxi 710075, China. Electronic address: 
      chenyulong.0901@stu.xjtu.edu.cn.
FAU - Liu, Huanhuan
AU  - Liu H
AD  - Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Institute of Basic and 
      Translational Medicine, Xi'an Medical University, Xi'an, Shaanxi 710021, China.
FAU - Wang, Xinhong
AU  - Wang X
AD  - The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong 
      University School of Medicine, Xi'an, Shaanxi 710004, China.
FAU - Zhang, Hongmei
AU  - Zhang H
AD  - The First Affiliated Hospital of Xi'an Medical University, Xi'an Medical 
      University, Xi'an, Shaanxi 710077, China.
FAU - Liu, Enqi
AU  - Liu E
AD  - Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, Xi'an, 
      Shaanxi 710061, China.
FAU - Su, Xingli
AU  - Su X
AD  - School of Basic and Medical Sciences, Xi'an Medical University, Xi'an, Shaanxi 
      710021, China. Electronic address: suxingli@xiyi.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170601
PL  - United States
TA  - Microvasc Res
JT  - Microvascular research
JID - 0165035
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Receptor, Endothelin A)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 2.7.11.24 (Mapk1 protein, rat)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 3.5.1.- (Sirt1 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Homocysteine/*pharmacology
MH  - Male
MH  - Mesenteric Artery, Superior/drug effects/enzymology
MH  - Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/antagonists & inhibitors/*metabolism
MH  - Muscle, Smooth, Vascular/*drug effects/enzymology
MH  - Myocytes, Smooth Muscle/*drug effects/enzymology
MH  - Phosphorylation
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Rats, Sprague-Dawley
MH  - Receptor, Endothelin A/*drug effects/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/antagonists & inhibitors/*metabolism
MH  - Up-Regulation
MH  - Vasoconstriction/drug effects
OTO - NOTNLM
OT  - Endothelin type A receptor
OT  - Extracellular signal related kinases 1 and 2
OT  - Homocysteine
OT  - Hyperhomocysteinemia
OT  - Sirtuin 1
EDAT- 2017/06/06 06:00
MHDA- 2018/05/15 06:00
CRDT- 2017/06/06 06:00
PHST- 2016/10/21 00:00 [received]
PHST- 2017/05/31 00:00 [revised]
PHST- 2017/05/31 00:00 [accepted]
PHST- 2017/06/06 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2017/06/06 06:00 [entrez]
AID - S0026-2862(16)30181-9 [pii]
AID - 10.1016/j.mvr.2017.05.010 [doi]
PST - ppublish
SO  - Microvasc Res. 2017 Nov;114:34-40. doi: 10.1016/j.mvr.2017.05.010. Epub 2017 Jun 
      1.