Open AccessPremature aging induced by radiation exhibits pro‐atherosclerotic effects mediated by epigenetic activation of CD 44 expression
Author(s) -
Lowe Donna,
Raj Kenneth
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12253
Subject(s) - biology , epigenetics , cd44 , disease , endothelium , microbiology and biotechnology , cancer research , immunology , endothelial dysfunction , dna damage , cell , gene , genetics , pathology , medicine , endocrinology , dna
Summary 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 CD 44 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 CD 44 expression is particularly significant as it causes persistent elevated CD 44 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.