title: The potential role of DNA methylation in the pathogenesis of abdominal aortic aneurysm.
abstract: Abdominal aortic aneurysm (AAA) is characterised by the chronic degradation and gradual, irreversible dilation of the abdominal aorta. Smoking, genetics, male sex and increased age are major factors associated with developing AAA. Rupture contributes to around 2% of deaths in all Caucasians over 65, and there is no pharmaco-therapeutic treatment. Methylation is an epigenetic modification to DNA, where a methyl group is added to a cytosine base 5' to a guanine (CpG dinucleotide). Methylation patterns are long term, inherited signatures that can induce changes in gene transcription, and can be affected by both genetic and environmental factors. Methylation changes are involved in hypertension and atherosclerosis, both of which are risk factors of, and often coexist with AAA. Extra-cellular matrix degradation and inflammation, both important pathological hallmarks of AAA, are also promoted by changes in CpG methylation in other diseases. Additionally, the adverse effects of smoking and ageing take place largely through epigenetic manipulation of the genome. Every factor associated with AAA appears to be associated with DNA methylation, yet no direct evidence confirms this. Future work to identify a link between global methylation and AAA, and differentially methylated regions may reveal valuable insight. The identification of a common epigenetic switching process may also signify a promising future for AAA pharmaco-therapeutic strategies. Epigenetic therapies are being designed to target pathogenic CpG methylation changes in other diseases, and it is feasible that these therapies may also be applicable to AAA in the future.
authors.affiliation: University of Leicester, Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK. Electronic address: bt96@le.ac.uk.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Toghill
authors.affiliation: University of Leicester, Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK.
authors.forename: Athanasios
authors.initials: A
authors.lastname: Saratzis
authors.affiliation: University of Leicester, Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK.
authors.forename: Seamus C
authors.initials: SC
authors.lastname: Harrison
authors.affiliation: University of Leicester, Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Verissimo
authors.affiliation: University of Leicester, Department of Biology, Leicester, UK.
authors.forename: Eamonn B
authors.initials: EB
authors.lastname: Mallon
authors.affiliation: University of Leicester, Department of Cardiovascular Sciences and the NIHR Leicester Cardiovascular Biomedical Research Unit, Leicester, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Bown
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics; D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology*; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D018899:CpG Islands; D019175:DNA Methylation; D004108:Dilatation, Pathologic; D044127:Epigenesis, Genetic; D020022:Genetic Predisposition to Disease; D006801:Humans; D010641:Phenotype; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
keywords: Abdominal aortic aneurysm; Cardiovascular disease; DNA methylation; Epigenome wide association; Inflammation; Matrix metalloproteinase