PMID- 18067449
OWN - NLM
STAT- MEDLINE
DCOM- 20080401
LR  - 20220223
IS  - 1434-6621 (Print)
IS  - 1434-6621 (Linking)
VI  - 45
IP  - 12
DP  - 2007
TI  - Hyperhomocysteinemia, DNA methylation and vascular disease.
PG  - 1660-6
AB  - Hyperhomocysteinemia (HHcy) has been established as a potent independent risk 
      factor for cardiovascular disease (CVD) and the underlying mechanism is largely 
      unknown. We were the first to propose that hypomethylation is the key biochemical 
      mechanism by which homocysteine (Hcy) inhibits endothelial cell (EC) growth. We 
      reported that clinically relevant concentrations of Hcy (10-50 micromol/L) exerts 
      highly selective inhibitory effects on cyclin A transcription and EC growth 
      through a hypomethylation related mechanism, which blocks cell cycle progression 
      and endothelium regeneration. Recently, we demonstrated that Hcy reduces DNA 
      methyltransferase 1 (DNMT1) activity and demethylates cyclin A promoter leading 
      to cyclin A chromatin remodeling. We found that adenovirus-transduced DNMT1 gene 
      expression reverses the inhibitory effect of Hcy on cyclin A expression and EC 
      growth inhibition. We hypothesize that DNA hypomethylation is a key biochemical 
      mechanism responsible for Hcy-induced cyclin A suppression and growth inhibition 
      in EC and contributes to CVD.
FAU - Jamaluddin, Md S
AU  - Jamaluddin MS
AD  - Department of Pharmacology, Temple University School of Medicine, Philadelphia, 
      PA 19140, USA.
FAU - Yang, Xiaofeng
AU  - Yang X
FAU - Wang, Hong
AU  - Wang H
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Germany
TA  - Clin Chem Lab Med
JT  - Clinical chemistry and laboratory medicine
JID - 9806306
RN  - 0 (Chromatin)
RN  - 0 (Cyclin A)
SB  - IM
MH  - Chromatin/metabolism
MH  - Cyclin A/genetics
MH  - *DNA Methylation
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/drug therapy/genetics
MH  - Promoter Regions, Genetic
MH  - Transcription, Genetic
MH  - Vascular Diseases/*complications/genetics
RF  - 51
EDAT- 2007/12/11 09:00
MHDA- 2008/04/02 09:00
CRDT- 2007/12/11 09:00
PHST- 2007/12/11 09:00 [pubmed]
PHST- 2008/04/02 09:00 [medline]
PHST- 2007/12/11 09:00 [entrez]
AID - 10.1515/CCLM.2007.350 [doi]
PST - ppublish
SO  - Clin Chem Lab Med. 2007;45(12):1660-6. doi: 10.1515/CCLM.2007.350.