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Title: DNA methylation polymorphisms precede any histological sign of atherosclerosis in mice lacking apolipoprotein E
Author: Lund, Gertrud
Andersson, Linda
Lauria, Massimiliano
Lindholm, Markus
Fraga, Mario F.
Villar Garea, Ana
Ballestar Tarín, Esteban
Esteller, Manel
Zaina, Silvio
Keywords: Apoproteïnes
Issue Date: 9-Jul-2004
Publisher: American Society for Biochemistry and Molecular Biology
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 APOE-null 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.
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It is part of: Journal of Biological Chemistry, 2004, vol. 279, num. 28, p. 29147-29154
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ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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