A post-exposure cohort study in Hiroshima and Nagasaki reported that low-dose exposure to radiation heightened the risk of
cardiovascular diseases (CVD), such as
stroke and
myocardial infarction, by 14-18% per Gy. Moreover, the risk of
atherosclerosis in the coronary arteries reportedly increases with
radiation therapy of the chest, including breast and
lung cancer treatment. Cellular senescence of vascular endothelial cells (ECs) is believed to play an important role in radiation-induced CVDs. The molecular mechanism of age-related cellular senescence is believed to involve
genomic instability and DNA damage response (DDR); the chronic
inflammation associated with senescence causes cardiovascular damage. Therefore, vascular endothelial cell senescence is believed to induce the pathogenesis of CVDs after radiation exposure. The findings of several prior studies have revealed that ionizing radiation (IR) induces cellular senescence as well as cell death in ECs. We have previously reported that DDR activates endothelial
nitric oxide (
NO) synthase, and NO production promotes endothelial senescence. Endothelial
NO synthase (eNOS) is a major
isoform expressed in ECs that maintains cardiovascular homeostasis. Therefore, radiation-induced NO production, a component of the DDR in ECs, may be involved in CVDs after radiation exposure. In this article, we describe the pathology of radiation-induced CVD and the unique radio-response to radiation exposure in ECs.