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Linda Andersson

Research engineer

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

Author

  • G Lund
  • Linda Andersson
  • M Lauria
  • Marie Lindholm
  • MF Fraga
  • A Villar-Garea
  • E Ballestar
  • M Esteller
  • S Zaina

Summary, in English

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.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis

Publishing year

2004

Language

English

Pages

29147-29154

Publication/Series

Journal of Biological Chemistry

Volume

279

Issue

28

Document type

Journal article

Publisher

ASBMB

Topic

  • Cardiac and Cardiovascular Systems

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 1083-351X