PMID- 20698860
OWN - NLM
STAT- MEDLINE
DCOM- 20110211
LR  - 20131121
IS  - 1440-1681 (Electronic)
IS  - 0305-1870 (Linking)
VI  - 37
IP  - 11
DP  - 2010 Nov
TI  - Homocysteine impaired endothelial function through compromised vascular 
      endothelial growth factor/Akt/endothelial nitric oxide synthase signalling.
PG  - 1071-7
LID - 10.1111/j.1440-1681.2010.05438.x [doi]
AB  - 1. Hyperhomocysteinaemia (HHcy) is associated with endothelial dysfunction and 
      has been recognized as a risk factor of cardiovascular disease. The present study 
      aimed to investigate the effect of homocysteine (Hcy) on endothelial function in 
      vivo and in vitro, and the underlying signalling pathways. 2. The HHcy animal 
      model was established by intragastric administration with l-methionine in rats. 
      Plasma Hcy and nitric oxide (NO) concentration were measured by fluorescence 
      immunoassay or nitrate reductase method, respectively. Vasorelaxation in response 
      to acetylcholine and sodium nitroprusside were carried out on aortic rings. Human 
      umbilical vein endothelial cells (HUVEC) were treated with indicated 
      concentrations of Hcy in the in vitro experiments. Intracellular NO level and NO 
      concentration in culture medium were assayed. The alterations of possible 
      signalling proteins were detected by western blot analysis. 3. l-methionine 
      administration induced a significant increase in plasma Hcy and decrease in 
      plasma NO. Endothelium-dependent relaxation of aortic rings in response to 
      acetylcholine was impaired in l-methionine-administrated rats. The in vitro study 
      showed that Hcy reduced both intracellular and culture medium NO levels. 
      Furthermore, Hcy decreased phosphorylation of endothelial nitric oxide synthase 
      (eNOS) at serine-1177 and phosphorylation of Akt at serine-473. Hcy-induced 
      dephosphorylation of eNOS at Ser-1177 was partially reversed by insulin (Akt 
      activator) and GF109203X (PKC inhibitor). Furthermore, Hcy reduced vascular 
      endothelial growth factor (VEGF) expression in a dose-dependent manner. 4. In 
      conclusion, Hcy impaired endothelial function through compromised 
      VEGF/Akt/endothelial nitric oxide synthase signalling. These findings will be 
      beneficial for further understanding the role of Hcy in cardiovascular disease.
CI  - (c) 2010 Blackwell Publishing Asia Pty Ltd.
FAU - Yan, Ting-Ting
AU  - Yan TT
AD  - Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen 
      University, Guangzhou, China.
FAU - Li, Qian
AU  - Li Q
FAU - Zhang, Xuan-Hong
AU  - Zhang XH
FAU - Wu, Wei-Kang
AU  - Wu WK
FAU - Sun, Juan
AU  - Sun J
FAU - Li, Lin
AU  - Li L
FAU - Zhang, Quan
AU  - Zhang Q
FAU - Tan, Hong-Mei
AU  - Tan HM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Australia
TA  - Clin Exp Pharmacol Physiol
JT  - Clinical and experimental pharmacology & physiology
JID - 0425076
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (vascular endothelial growth factor A, rat)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Aorta, Thoracic/drug effects/metabolism
MH  - Blotting, Western
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Endothelium, Vascular/enzymology/metabolism/*physiology
MH  - Homocysteine/blood/*pharmacology
MH  - Humans
MH  - Hyperhomocysteinemia/blood/enzymology/metabolism/*physiopathology
MH  - Male
MH  - Methionine
MH  - Nitric Oxide/biosynthesis/blood
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Vascular Endothelial Growth Factor A/*metabolism
MH  - Vasodilation/drug effects/physiology
EDAT- 2010/08/12 06:00
MHDA- 2011/02/12 06:00
CRDT- 2010/08/12 06:00
PHST- 2010/08/12 06:00 [entrez]
PHST- 2010/08/12 06:00 [pubmed]
PHST- 2011/02/12 06:00 [medline]
AID - CEP5438 [pii]
AID - 10.1111/j.1440-1681.2010.05438.x [doi]
PST - ppublish
SO  - Clin Exp Pharmacol Physiol. 2010 Nov;37(11):1071-7. doi: 
      10.1111/j.1440-1681.2010.05438.x.