PMID- 23497786
OWN - NLM
STAT- MEDLINE
DCOM- 20131021
LR  - 20151119
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 228
IP  - 2
DP  - 2013 Jun
TI  - The potential role of homocysteine mediated DNA methylation and associated 
      epigenetic changes in abdominal aortic aneurysm formation.
PG  - 295-305
LID - S0021-9150(13)00129-9 [pii]
LID - 10.1016/j.atherosclerosis.2013.02.019 [doi]
AB  - Previous studies have suggested that homocysteine (Hcy) has wide-ranging 
      biological effects, including accelerating atherosclerosis, impairing post injury 
      endothelial repair and function, deregulating lipid metabolism and inducing 
      thrombosis. However, the biochemical basis by which hyperhomocysteinemia (HHcy) 
      contributes to cardiovascular diseases (CVDs) remains largely unknown. Several 
      case-control studies have reported an association between HHcy and the presence 
      of abdominal aortic aneurysms (AAA) and there are supportive data from animal 
      models. Genotypic data concerning the association between variants of genes 
      involved in the methionine cycle and AAA are conflicting probably due to problems 
      such as reverse causality and confounding. The multifactorial nature of AAA 
      suggests the involvement of additional epigenetic factors in disease formation. 
      Elevated Hcy levels have been previously linked to altered DNA methylation levels 
      in various diseases. Folate or vitamin B12 based methods of lowering Hcy have had 
      disappointingly limited effects in reducing CVD events. One possible reason for 
      the limited efficacy of such therapy is that they have failed to reverse 
      epigenetic changes induced by HHcy. It is possible that individuals with HHcy 
      have an "Hcy memory effect" due to epigenetic alterations which continue to 
      promote progression of cardiovascular complications even after Hcy levels are 
      lowered. It is possible that deleterious effect of prior, extended exposure to 
      elevated Hcy concentrations have long-lasting effects on target organs and genes, 
      hence underestimating the benefit of Hcy lowering therapies in CVD patients. 
      Therapies targeting the epigenetic machinery as well as lowering circulating Hcy 
      concentrations may have a more efficacious effect in reducing the incidence of 
      cardiovascular complications.
CI  - Copyright (c) 2013 Elsevier Ireland Ltd. All rights reserved.
FAU - Krishna, Smriti Murali
AU  - Krishna SM
AD  - The Vascular Biology Unit, Queensland Research Centre for Peripheral Vascular 
      Disease, School of Medicine and Dentistry, James Cook University, James Cook 
      Drive, Douglas, Townsville, QLD 4811, Australia.
FAU - Dear, Anthony
AU  - Dear A
FAU - Craig, Jeffrey M
AU  - Craig JM
FAU - Norman, Paul E
AU  - Norman PE
FAU - Golledge, Jonathan
AU  - Golledge J
LA  - eng
GR  - Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130226
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (Biomarkers)
RN  - 0 (Histones)
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Aortic Aneurysm, Abdominal/*blood/epidemiology/*genetics/therapy
MH  - Biomarkers/blood
MH  - *DNA Methylation
MH  - *Epigenesis, Genetic
MH  - Genetic Predisposition to Disease
MH  - Genetic Therapy
MH  - Histones/metabolism
MH  - Homocysteine/*blood
MH  - Humans
MH  - Phenotype
MH  - Prognosis
MH  - Risk Factors
MH  - Up-Regulation
EDAT- 2013/03/19 06:00
MHDA- 2013/10/22 06:00
CRDT- 2013/03/19 06:00
PHST- 2013/01/16 00:00 [received]
PHST- 2013/02/08 00:00 [revised]
PHST- 2013/02/08 00:00 [accepted]
PHST- 2013/03/19 06:00 [entrez]
PHST- 2013/03/19 06:00 [pubmed]
PHST- 2013/10/22 06:00 [medline]
AID - S0021-9150(13)00129-9 [pii]
AID - 10.1016/j.atherosclerosis.2013.02.019 [doi]
PST - ppublish
SO  - Atherosclerosis. 2013 Jun;228(2):295-305. doi: 
      10.1016/j.atherosclerosis.2013.02.019. Epub 2013 Feb 26.