PMID- 15704255
OWN - NLM
STAT- MEDLINE
DCOM- 20050725
LR  - 20231213
IS  - 0145-5680 (Print)
IS  - 0145-5680 (Linking)
VI  - 50
IP  - 8
DP  - 2004 Dec
TI  - The role of hyperhomocysteinemia in nitric oxide (NO) and endothelium-derived 
      hyperpolarizing factor (EDHF)-mediated vasodilatation.
PG  - 911-6
AB  - Hyperhomocysteinemia (HHcy) is associated with impaired endothelial-dependent 
      vasodilatation and increased risk of atherosclerosis and thrombosis. Here, we 
      summarize some of our previous work on the effect of HHcy on pathways involved in 
      endothelium-dependent vasodilatation, and present new data concerning the 
      endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation. We 
      showed that the 894 G>T single-nucleotide polymorphism in the human endothelial 
      nitric oxide synthase gene (eNOS) increased the risk of recurrent venous 
      thrombosis in individuals with elevated homocysteine levels, indicating that the 
      pathophysiological mechanism in HHcy involves impaired NO-mediated 
      vasodilatation. In addition, the EDHF-mediated vasodilatation of the renal artery 
      was disturbed in diet-induced hyperhomocysteinemic rats. Interestingly, we 
      demonstrated that pretreatment of rats with periodate-oxidized adenosine (Adox), 
      which is an inhibitor of S-adenosylhomocysteine hydrolase, prevented the 
      methionine-induced rise in plasma total Hcy (tHcy) levels but not the inhibition 
      of the EDHF pathway. Furthermore, we demonstrated that S-adenosylhomocysteine 
      (AdoHcy) and S-adenosylmethionine (AdoMet) levels were increased in the kidneys 
      of diet-induced HHcy rats, resulting in a decreased AdoMet:AdoHcy ratio. In 
      addition, we demonstrated that mRNA expression of Connexin 40, which is one of 
      the structural subunits of gap-junctions, was down-regulated in endothelial cells 
      of HHcy rats, and correlated with elevated AdoHcy levels in kidney of these rats. 
      These finding suggest a key role for AdoHcy in relation to decreased Cx40 mRNA 
      expression and impaired EDHF-mediated vasodilatation of HHcy rats.
FAU - Heil, S G
AU  - Heil SG
AD  - Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical 
      Centre, 6500 HB Nijmegen, The Netherlands. s.heil@cukz.umcn.nl
FAU - De Vriese, A S
AU  - De Vriese AS
FAU - Kluijtmans, L A J
AU  - Kluijtmans LA
FAU - Mortier, S
AU  - Mortier S
FAU - Den Heijer, M
AU  - Den Heijer M
FAU - Blom, H J
AU  - Blom HJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - France
TA  - Cell Mol Biol (Noisy-le-grand)
JT  - Cellular and molecular biology (Noisy-le-Grand, France)
JID - 9216789
RN  - 0 (Biological Factors)
RN  - 0 (Connexins)
RN  - 0 (RNA, Messenger)
RN  - 0 (endothelium-dependent hyperpolarization factor)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 979-92-0 (S-Adenosylhomocysteine)
SB  - IM
MH  - Animals
MH  - Biological Factors/*metabolism
MH  - Connexins/metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Gap Junctions
MH  - Humans
MH  - Hyperhomocysteinemia/*metabolism
MH  - Kidney/metabolism
MH  - Models, Biological
MH  - Nitric Oxide/*metabolism
MH  - Odds Ratio
MH  - Oxidative Stress
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - S-Adenosylhomocysteine/metabolism
MH  - Time Factors
MH  - Vasodilation
MH  - Venous Thrombosis/metabolism
MH  - Gap Junction alpha-5 Protein
RF  - 43
EDAT- 2005/02/11 09:00
MHDA- 2005/07/26 09:00
CRDT- 2005/02/11 09:00
PHST- 2005/02/11 09:00 [pubmed]
PHST- 2005/07/26 09:00 [medline]
PHST- 2005/02/11 09:00 [entrez]
PST - ppublish
SO  - Cell Mol Biol (Noisy-le-grand). 2004 Dec;50(8):911-6.