PMID- 20858749
OWN - NLM
STAT- MEDLINE
DCOM- 20101228
LR  - 20231213
IS  - 1522-1555 (Electronic)
IS  - 0193-1849 (Linking)
VI  - 299
IP  - 6
DP  - 2010 Dec
TI  - Homocysteine impairs coronary artery endothelial function by inhibiting 
      tetrahydrobiopterin in patients with hyperhomocysteinemia.
PG  - E1061-5
LID - 10.1152/ajpendo.00367.2010 [doi]
AB  - Hyperhomocysteinemia (HHcy) has been associated with impaired vascular 
      endothelial function. Our previous study demonstrated significantly higher 
      secretion of the chemokine monocyte chemoattractant protein-1 from monocytes in 
      response to lipopolysaccharide in patients with HHcy. In the present study, we 
      investigated whether coronary endothelial function was damaged in patients with 
      chronic HHcy (plasma level of homocysteine >15 mumol/l) and, if so, whether this 
      impaired endothelial function is induced by the uncoupling of endothelial nitric 
      oxide synthase (eNOS). When tetrahydrobiopterin levels are inadequate, eNOS is no 
      longer coupled to l-arginine oxidation, which results in reactive oxygen species 
      rather than nitric oxide production, thereby inducing vascular endothelial 
      dysfunction. The 71 participants were divided into two groups, control (n = 50) 
      and HHcy (n = 21). Quantification of coronary flow velocity reserve (CFVR) was 
      after rest and after adenosine administration done by noninvasive Doppler 
      echocardiography. Plasma levels of nitric oxide and tetrahydrobiopterin were 
      significantly lower in patients with HHcy than in controls (99.54 +/- 32.23 vs. 
      119.50 +/- 37.68 mumol/l and 1.43 +/- 0.46 vs. 1.73 +/- 0.56 pmol/ml, all P < 0.05). 
      Furthermore, CFVR was significantly lower in the HHcy than the control group 
      (2.76 +/- 0.49 vs. 3.09 +/- 0.52, P < 0.05). In addition, plasma level of 
      homocysteine was negatively correlated with CFVR. Chronic HHcy may contribute to 
      coronary artery disease by inducing dysfunction of the coronary artery 
      endothelium. The uncoupling of eNOS induced by HHcy in patients with chronic HHcy 
      may explain this adverse effect in part.
FAU - He, Liyun
AU  - He L
AD  - Dept. of Endocrinology, Peking University Health Science Center, Beijing 100191, 
      People's Republic of China.
FAU - Zeng, Hui
AU  - Zeng H
FAU - Li, Fuwang
AU  - Li F
FAU - Feng, Jieli
AU  - Feng J
FAU - Liu, Shan
AU  - Liu S
FAU - Liu, Jinbo
AU  - Liu J
FAU - Yu, Jie
AU  - Yu J
FAU - Mao, Jieming
AU  - Mao J
FAU - Hong, Tianpei
AU  - Hong T
FAU - Chen, Alex F
AU  - Chen AF
FAU - Wang, Xian
AU  - Wang X
FAU - Wang, Guang
AU  - Wang G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100921
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 0 (Biopterins)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EGX657432I (sapropterin)
SB  - IM
CIN - Am J Physiol Endocrinol Metab. 2011 Jun;300(6):E1176; author reply E1177-8. PMID: 
      21427414
MH  - Adult
MH  - Aged
MH  - Biopterins/*analogs & derivatives/metabolism
MH  - Blood Flow Velocity
MH  - Chromatography, High Pressure Liquid
MH  - Coronary Vessels/metabolism/*physiopathology
MH  - Endothelium, Vascular/metabolism/*physiopathology
MH  - Female
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/metabolism/*physiopathology
MH  - Male
MH  - Middle Aged
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Statistics, Nonparametric
EDAT- 2010/09/23 06:00
MHDA- 2010/12/29 06:00
CRDT- 2010/09/23 06:00
PHST- 2010/09/23 06:00 [entrez]
PHST- 2010/09/23 06:00 [pubmed]
PHST- 2010/12/29 06:00 [medline]
AID - ajpendo.00367.2010 [pii]
AID - 10.1152/ajpendo.00367.2010 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2010 Dec;299(6):E1061-5. doi: 
      10.1152/ajpendo.00367.2010. Epub 2010 Sep 21.