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DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E

Lund, G; Andersson, Linda LU ; Lauria, M; Lindholm, Marie LU ; Fraga, MF; Villar-Garea, A; Ballestar, E; Esteller, M and Zaina, S (2004) In Journal of Biological Chemistry 279(28). p.29147-29154
Abstract
The present work investigates the occurrence and significance of aberrant DNA methylation patterns during early stages of atherosclerosis. To this end, we asked whether the genetically atherosclerosis-prone APOEnull mice show any changes in DNA methylation patterns before the appearance of histologically detectable vascular lesion. We exploited a combination of various techniques: DNA fingerprinting, in vitro methyl-accepting assay, 5-methylcytosine quantitation, histone post-translational modification analysis, Southern blotting, and PCR. Our results show that alterations in DNA methylation profiles, including both hyper- and hypomethylation, were present in aortas and PBMC of 4-week-old mutant mice with no detectable atherosclerotic... (More)
The present work investigates the occurrence and significance of aberrant DNA methylation patterns during early stages of atherosclerosis. To this end, we asked whether the genetically atherosclerosis-prone APOEnull mice show any changes in DNA methylation patterns before the appearance of histologically detectable vascular lesion. We exploited a combination of various techniques: DNA fingerprinting, in vitro methyl-accepting assay, 5-methylcytosine quantitation, histone post-translational modification analysis, Southern blotting, and PCR. Our results show that alterations in DNA methylation profiles, including both hyper- and hypomethylation, were present in aortas and PBMC of 4-week-old mutant mice with no detectable atherosclerotic lesion. Sequencing and expression analysis of 60 leukocytic polymorphisms revealed that epigenetic changes involve transcribed genic sequences, as well as repeated interspersed elements. Furthermore, we showed for the first time that atherogenic lipoproteins promote global DNA hypermethylation in a human monocyte cell line. Taken together, our results unequivocally show that alterations in DNA methylation profiles are early markers of atherosclerosis in a mouse model and may play a causative role in atherogenesis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
279
issue
28
pages
29147 - 29154
publisher
ASBMB
external identifiers
  • wos:000222445300040
  • scopus:3142672297
ISSN
1083-351X
DOI
10.1074/jbc.M403618200
language
English
LU publication?
yes
id
d2990ca6-5bae-4f6f-bb78-69cbbc3b78a8 (old id 273511)
date added to LUP
2007-10-24 20:59:04
date last changed
2017-11-19 03:39:28
@article{d2990ca6-5bae-4f6f-bb78-69cbbc3b78a8,
  abstract     = {The present work investigates the occurrence and significance of aberrant DNA methylation patterns during early stages of atherosclerosis. To this end, we asked whether the genetically atherosclerosis-prone APOEnull mice show any changes in DNA methylation patterns before the appearance of histologically detectable vascular lesion. We exploited a combination of various techniques: DNA fingerprinting, in vitro methyl-accepting assay, 5-methylcytosine quantitation, histone post-translational modification analysis, Southern blotting, and PCR. Our results show that alterations in DNA methylation profiles, including both hyper- and hypomethylation, were present in aortas and PBMC of 4-week-old mutant mice with no detectable atherosclerotic lesion. Sequencing and expression analysis of 60 leukocytic polymorphisms revealed that epigenetic changes involve transcribed genic sequences, as well as repeated interspersed elements. Furthermore, we showed for the first time that atherogenic lipoproteins promote global DNA hypermethylation in a human monocyte cell line. Taken together, our results unequivocally show that alterations in DNA methylation profiles are early markers of atherosclerosis in a mouse model and may play a causative role in atherogenesis.},
  author       = {Lund, G and Andersson, Linda and Lauria, M and Lindholm, Marie and Fraga, MF and Villar-Garea, A and Ballestar, E and Esteller, M and Zaina, S},
  issn         = {1083-351X},
  language     = {eng},
  number       = {28},
  pages        = {29147--29154},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E},
  url          = {http://dx.doi.org/10.1074/jbc.M403618200},
  volume       = {279},
  year         = {2004},
}