DNA damage response in vascular endothelial senescence: Implication for radiation-induced cardiovascular diseases

Abstract

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.

Hydrogels for the treatment of radiation-induced skin and mucosa damages: An up-to-date overview

“…Endothelial cells contain extremely high levels of ceramide synthase and acidic sphingomyelinase, a large amount of which produce ceramides by radiation in the cell, resulting in subsequent apoptosis and microvascular endothelial cell loss (Lee et al, 2013). Studies have shown that even lower doses of radiation could induce endothelial ceramide production, inducing apoptosis of bovine aortic endothelial cells (Nagane et al, 2021;Tapio et al, 2021). At the same time, inadequate blood supply is a key problem resulting in the difficulty of radiation-induced skin and mucosa wounds healing, mainly manifested by the lack of microvascularization and delayed granulation tissue formation (Paderno et al, 2016).…”

Tissue Reactions and Mechanism in Cardiovascular Diseases Induced by Radiation

“…The initial events of radiation-induced atherosclerosis are endothelial cell damage and the migration of monocytes into the intima, followed by the uptake of LDL and the formation of distinct streaks. Radiation-induced DNA damage, especially DSB, is a major cause of cell death, senescence, and the dysregulation of proliferation and differentiation [ 129 ]. Furthermore, oxidative stress is a substantial contributor to radiation-induced senescence, as well as radiation-induced DNA damage and faster telomere attrition [ 129 , 130 , 131 , 132 , 133 ].…”

“…Radiation-induced DNA damage, especially DSB, is a major cause of cell death, senescence, and the dysregulation of proliferation and differentiation [ 129 ]. Furthermore, oxidative stress is a substantial contributor to radiation-induced senescence, as well as radiation-induced DNA damage and faster telomere attrition [ 129 , 130 , 131 , 132 , 133 ]. IR has been proven in multiple in vitro investigations to promote endothelial cell senescence, primarily by increasing doses of radiation [ 134 , 135 ].…”

Low Dose and Non-Targeted Radiation Effects in Environmental Protection and Medicine—A New Model Focusing on Electromagnetic Signaling

“…In the case of low dose radiation exposures, cancer, cardiovascular disease, foetal abnormality, and chronic fatigue are examples of gross adverse effects [ 89 ]. These are thought to result from genomic instability, mutation in critical genes, microenvironment alterations leading to niche compromise, haematological insufficiency and immune dysfunction [ 7 , 29 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ]. These in turn are attributed to DNA damage, elevated ROS, mitochondrial insufficiency, membrane channel imbalances and failure of “checks and balances” on the rate of specific enzyme reactions, leading to tipping points where metabolic malfunction occurs.…”