PMID- 21614558
OWN - NLM
STAT- MEDLINE
DCOM- 20121001
LR  - 20211020
IS  - 1438-2199 (Electronic)
IS  - 0939-4451 (Print)
IS  - 0939-4451 (Linking)
VI  - 42
IP  - 5
DP  - 2012 May
TI  - Cellular hypomethylation is associated with impaired nitric oxide production by 
      cultured human endothelial cells.
PG  - 1903-11
LID - 10.1007/s00726-011-0916-0 [doi]
AB  - Hyperhomocysteinemia (HHcy) is a risk factor for vascular disease, but the 
      underlying mechanisms remain incompletely defined. Reduced bioavailability of 
      nitric oxide (NO) is a principal manifestation of underlying endothelial 
      dysfunction, which is an initial event in vascular disease. Inhibition of 
      cellular methylation reactions by S-adenosylhomocysteine (AdoHcy), which 
      accumulates during HHcy, has been suggested to contribute to vascular 
      dysfunction. However, thus far, the effect of intracellular AdoHcy accumulation 
      on NO bioavailability has not yet been fully substantiated by experimental 
      evidence. The present study was carried out to evaluate whether disturbances in 
      cellular methylation status affect NO production by cultured human endothelial 
      cells. Here, we show that a hypomethylating environment, induced by the 
      accumulation of AdoHcy, impairs NO production. Consistent with this finding, we 
      observed decreased eNOS expression and activity, but, by contrast, enhanced NOS3 
      transcription. Taken together, our data support the existence of regulatory 
      post-transcriptional mechanisms modulated by cellular methylation potential 
      leading to impaired NO production by cultured human endothelial cells. As such, 
      our conclusions may have implications for the HHcy-mediated reductions in NO 
      bioavailability and endothelial dysfunction.
FAU - Barroso, M
AU  - Barroso M
AD  - Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty 
      of Pharmacy, University of Lisbon, Lisbon, Portugal.
FAU - Rocha, M S
AU  - Rocha MS
FAU - Esse, R
AU  - Esse R
FAU - Goncalves, I Jr
AU  - Goncalves I Jr
FAU - Gomes, A Q
AU  - Gomes AQ
FAU - Teerlink, T
AU  - Teerlink T
FAU - Jakobs, C
AU  - Jakobs C
FAU - Blom, H J
AU  - Blom HJ
FAU - Loscalzo, J
AU  - Loscalzo J
FAU - Rivera, I
AU  - Rivera I
FAU - de Almeida, I Tavares
AU  - de Almeida IT
FAU - Castro, R
AU  - Castro R
LA  - eng
GR  - U54 HL070819/HL/NHLBI NIH HHS/United States
GR  - P01 HL048743/HL/NHLBI NIH HHS/United States
GR  - R01 HL061795/HL/NHLBI NIH HHS/United States
GR  - HL48743/HL/NHLBI NIH HHS/United States
GR  - R37 HL061795/HL/NHLBI NIH HHS/United States
GR  - HL81587/HL/NHLBI NIH HHS/United States
GR  - P01 HL081587/HL/NHLBI NIH HHS/United States
GR  - HL70819/HL/NHLBI NIH HHS/United States
GR  - HL61795/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110526
PL  - Austria
TA  - Amino Acids
JT  - Amino acids
JID - 9200312
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 63CV1GEK3Y (N,N-dimethylarginine)
RN  - 94ZLA3W45F (Arginine)
RN  - 979-92-0 (S-Adenosylhomocysteine)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
SB  - IM
MH  - Arginine/*analogs & derivatives/metabolism
MH  - Cells, Cultured
MH  - Endothelial Cells/*metabolism
MH  - Gene Expression Regulation
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Hyperhomocysteinemia/metabolism
MH  - *Methylation
MH  - Nitric Oxide/deficiency/*metabolism
MH  - Nitric Oxide Synthase Type III/antagonists & inhibitors/metabolism
MH  - S-Adenosylhomocysteine/*metabolism
MH  - Vascular Diseases/metabolism
PMC - PMC3602903
MID - NIHMS449692
EDAT- 2011/05/27 06:00
MHDA- 2012/10/02 06:00
PMCR- 2013/03/20
CRDT- 2011/05/27 06:00
PHST- 2010/11/08 00:00 [received]
PHST- 2011/04/08 00:00 [accepted]
PHST- 2011/05/27 06:00 [entrez]
PHST- 2011/05/27 06:00 [pubmed]
PHST- 2012/10/02 06:00 [medline]
PHST- 2013/03/20 00:00 [pmc-release]
AID - 10.1007/s00726-011-0916-0 [doi]
PST - ppublish
SO  - Amino Acids. 2012 May;42(5):1903-11. doi: 10.1007/s00726-011-0916-0. Epub 2011 
      May 26.