Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression.
Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression.
复制标题
作者：
Lowe D;Raj K
Age is undoubtedly a major risk factor for heart disease. However, the reason for this is not entirely clear. In the course of our investigation into the mechanism of radiation-induced cardiovascular disease, we made several unexpected findings that inform us on this question. We observed that human coronary endothelial cells, while being able to initiate repair of radiation-induced DNA damage, often fail to complete the repair and become senescent. Such radiation-induced cellular aging occurs through a mutation-independent route. Endothelial cells that aged naturally through replication or as a result of radiation exhibited indistinguishable characteristics. The promoter regions of the CD44 gene in aging endothelial cells become demethylated, and the proteins are highly expressed on the cell surface, making the cells adhesive for monocytes. Adhesion is a cardinal feature that recruits monocytes to the endothelium, allowing them to infiltrate the vessel wall and initiate atherosclerosis. The epigenetic activation of CD44 expression is particularly significant as it causes persistent elevated CD44 protein expression, making senescent endothelial cells chronically adhesive. In addition to understanding why cardiovascular disease increases with age, these observations provide insights into the puzzling association between radiation and cardiovascular disease and highlight the need to consider premature aging as an additional risk of radiation to human health.
登录
查看更多内容
影响因子：
3.4
作者：
Ellender, M;Harrison, JD;Cox, R
通讯作者：
Cox, R
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P
DOI：
10.1152/ajpheart.00835.2009
发表时间：
2010-06-01
影响因子：
4.8
作者：
Mun, Gyeong In;Boo, Yong Chool
通讯作者：
Boo, Yong Chool
影响因子：
6
作者：
Kagara, Naofumi;Huynh, Kelly T.;Hoon, Dave S. B.
通讯作者：
Hoon, Dave S. B.
DOI：
10.1016/j.ijrobp.2008.02.031
发表时间：
2008-07-01
影响因子：
7
作者：
Hoving, Saske;Heeneman, Sylvia;Stewart, Fiona A.
通讯作者：
Stewart, Fiona A.