作者
Ernest Diez Benavente, Robin JG Hartman, Tim R Sakkers, Marian Wesseling, Yannicke Sloots, Lotte Slenders, Arjan Boltjes, Barend M Mol, Gert J de Borst, Dominique PV de Kleijn, Koen HM Prange, Menno PJ de Winther, Johan Kuiper, Mete Civelek, Sander W van der Laan, Steve Horvath, N Charlotte Onland-Moret, Michal Mokry, Gerard Pasterkamp, Hester M den Ruijter
发表日期
2024/6
期刊
Arteriosclerosis, Thrombosis, and Vascular Biology
卷号
44
期号
6
页码范围
1419-1431
出版商
Lippincott Williams & Wilkins
简介
BACKGROUND
Epigenetic age estimators (clocks) are predictive of human mortality risk. However, it is not yet known whether the epigenetic age of atherosclerotic plaques is predictive for the risk of cardiovascular events.
METHODS
Whole-genome DNA methylation of human carotid atherosclerotic plaques (n=485) and of blood (n=93) from the Athero-Express endarterectomy cohort was used to calculate epigenetic age acceleration (EAA). EAA was linked to clinical characteristics, plaque histology, and future cardiovascular events (n=136). We studied whole-genome DNA methylation and bulk and single-cell transcriptomics to uncover molecular mechanisms of plaque EAA. We experimentally confirmed our in silico findings using in vitro experiments in primary human coronary endothelial cells.
RESULTS
Male and female patients with severe atherosclerosis had a median chronological age of 69 years. The …
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