Dynamic epigenetic age mosaicism in the human atherosclerotic artery
Zaina, Silvio ; Esteller, Manel ; Gonçalves, Isabel LU
and Lund, Gertrud
(2022)
In PLoS ONE
17(6 June).
- Abstract
Accelerated epigenetic ageing, a promising marker of disease risk, has been detected in peripheral blood cells of atherosclerotic patients, but evidence in the vascular wall is lacking. Understanding the trends of epigenetic ageing in the atheroma may provide insights into mechanisms of atherogenesis or identify targets for molecular therapy. We surveyed DNA methylation age in two human artery samples: a set of donor-matched, paired atherosclerotic and healthy aortic portions, and a set of carotid artery atheromas. The well-characterized pan-tissue Horvath epigenetic clock was used, together with the Weidner whole-blood-specific clock as validation. For the first time, we document dynamic DNA methylation age mosaicism of the vascular... (More)
Accelerated epigenetic ageing, a promising marker of disease risk, has been detected in peripheral blood cells of atherosclerotic patients, but evidence in the vascular wall is lacking. Understanding the trends of epigenetic ageing in the atheroma may provide insights into mechanisms of atherogenesis or identify targets for molecular therapy. We surveyed DNA methylation age in two human artery samples: a set of donor-matched, paired atherosclerotic and healthy aortic portions, and a set of carotid artery atheromas. The well-characterized pan-tissue Horvath epigenetic clock was used, together with the Weidner whole-blood-specific clock as validation. For the first time, we document dynamic DNA methylation age mosaicism of the vascular wall that is atherosclerosis-related, switches from acceleration to deceleration with chronological ageing, and is consistent in human aorta and carotid atheroma. At CpG level, the Horvath epigenetic clock showed modest differential methylation between atherosclerotic and healthy aortic portions, weak association with atheroma histological grade and no clear evidence for participation in atherosclerosis-related cellular pathways. Our data suggest caution when assigning a unidirectional DNA methylation age change to the atherosclerotic arterial wall. Also, the results support previous conclusions that epigenetic ageing reflects non-disease-specific cellular alterations.
(Less)
- author
- Zaina, Silvio
; Esteller, Manel
; Gonçalves, Isabel
LU
and Lund, Gertrud
- organization
- publishing date
- 2022-06
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 17
- issue
- 6 June
- article number
- e0269501
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:35657981
- scopus:85131702041
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0269501
- language
- English
- LU publication?
- yes
- id
- 21a513d9-66f2-4f5d-964d-6200ad2e85da
- date added to LUP
- 2022-09-06 12:48:15
- date last changed
- 2025-02-21 20:26:55
@article{21a513d9-66f2-4f5d-964d-6200ad2e85da,
abstract = {{<p>Accelerated epigenetic ageing, a promising marker of disease risk, has been detected in peripheral blood cells of atherosclerotic patients, but evidence in the vascular wall is lacking. Understanding the trends of epigenetic ageing in the atheroma may provide insights into mechanisms of atherogenesis or identify targets for molecular therapy. We surveyed DNA methylation age in two human artery samples: a set of donor-matched, paired atherosclerotic and healthy aortic portions, and a set of carotid artery atheromas. The well-characterized pan-tissue Horvath epigenetic clock was used, together with the Weidner whole-blood-specific clock as validation. For the first time, we document dynamic DNA methylation age mosaicism of the vascular wall that is atherosclerosis-related, switches from acceleration to deceleration with chronological ageing, and is consistent in human aorta and carotid atheroma. At CpG level, the Horvath epigenetic clock showed modest differential methylation between atherosclerotic and healthy aortic portions, weak association with atheroma histological grade and no clear evidence for participation in atherosclerosis-related cellular pathways. Our data suggest caution when assigning a unidirectional DNA methylation age change to the atherosclerotic arterial wall. Also, the results support previous conclusions that epigenetic ageing reflects non-disease-specific cellular alterations.</p>}},
author = {{Zaina, Silvio and Esteller, Manel and Gonçalves, Isabel and Lund, Gertrud}},
issn = {{1932-6203}},
language = {{eng}},
number = {{6 June}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Dynamic epigenetic age mosaicism in the human atherosclerotic artery}},
url = {{http://dx.doi.org/10.1371/journal.pone.0269501}},
doi = {{10.1371/journal.pone.0269501}},
volume = {{17}},
year = {{2022}},
}