Journal
ATHEROSCLEROSIS
Volume 212, Issue 1, Pages 16-29Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2010.02.008
Keywords
Abdominal aortic aneurysm; Epigenetics; DNA methylation; Histone modifications; Epigenetic therapy
Funding
- National Institute of Health, USA [RO1 HL080010]
- Townsville Hospital
- National Health and Medical Research Council [540403, 540404, 540405]
- National Health and Medical Research Council, Australia [431503, 458505]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL080010] Funding Source: NIH RePORTER
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Abdominal aortic aneurysm (AAA) is a common disease associated with significant cardiovascular morbidity and mortality. The pathogenesis of AAA is poorly defined, making targeting of new therapies problematic. Current evidence favours an interaction of multiple environmental and genetic factors in the initiation and progression of AAA. Epigenetics is the term used to define the properties of the genome that are not explained by the primary sequence, but are due to the modifications of DNA and/or associated proteins. Previous research indicates the association of gene specific promoter DNA hyper-methylation and global DNA hypo-methylation with atherosclerosis. Evidence also suggests an important role for epigenetic processes such as histone acetylation in cardiovascular diseases including atherosclerosis and restenosis. Altered DNA methylation or histone acetylation occur in inflammation, cellular proliferation and remodelling processes and therefore maybe relevant to the pathology of AAA. Important risk factors for AAA, including cigarette smoking, older age, male gender and hypertension, have been linked with epigenetic effects and thus could act in this way to promote AAA. In this review, we discuss the potential role of epigenetic mechanisms in AAA. Since epigenetic alterations are to some extent reversible, further study of this area may identify new treatment targets for AAA. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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