Ionizing Irradiation Induces Vascular Damage in the Aorta of Wild-Type Mice

Abstract

There has been a recent upsurge of interest in the effects of ionizing radiation exposure on the circulatory system, because a mounting body of epidemiological evidence suggests that irradiation induces cardio- and cerebrovascular disease at a much lower dose and lower dose rate than previously considered. The goal of our project is to determine whether dose protraction alters radiation effects on the circulatory system in a mouse model. To this end, the use of wild-type mice is pivotal albeit without manifestation of vascular diseases, because disease models (e.g., apolipoprotein E-deficient mice) are prone to hormetic responses following protracted exposures. As such, here, we first set out to analyze prelesional changes in the descending thoracic aorta of wild-type mice up to six months after a single acute exposure to 0 or 5 Gy of 137Cs γ-rays. Scanning electron microscopy demonstrated that irradiation facilitated structural disorganizations and detachment of the aortic endothelium. The Miles assay with an albumin-binding dye Evans Blue revealed that irradiation enhanced vascular permeability. Immunofluorescence staining showed that irradiation led to partial loss of the aortic endothelium (evidenced by a lack of adhesion molecule CD31 and 4′,6-diamidino-2-phenylindole (DAPI) signals), a decrease in endothelial nitric oxide synthase and adherens junction protein (vascular endothelial (VE)-cadherin) in the aortic endothelium, along with an increase in inflammation (tumor necrosis factor (TNF)-α) and macrophage (F4/80) markers in the aorta. These findings suggest that irradiation produces vascular damage manifested as endothelial cell loss and increased vascular permeability, and that the decreased adherens junction and the increased inflammation lead to macrophage recruitment implicated in the early stage of atherosclerosis.

Exposure to Low to Moderate Doses of Ionizing Radiation Induces A Reduction of Pro-Inflammatory Ly6chigh Monocytes and a U-Curved Response of T Cells in APOE -/- Mice

“…Despite multiple studies investigating the health impacts of ionizing radiation, questions remain regarding the effects of exposure on cardiovascular diseases. Both epidemiological [1][2][3][4] and experimental studies [5][6][7][8][9][10][11] revealed that exposure to high doses of ionizing radiation has detrimental cardiovascular outcomes. However, when it comes to low dose ionizing radiation (LDIR), epidemiological studies have not provided a clear message.…”

Exosomes derived from plasma: promising immunomodulatory agents for promoting angiogenesis to treat radiation-induced vascular dysfunction

“…However, it is a double-edged sword, downregulating angiogenesis and interrupting normal wound healing and bone defect repair. Numerous researchers have investigated radiation-associated vascular dysfunction and found that radiation causes endothelial cell apoptosis ( Paris et al, 2001 ), promotes structural disorganization and detachment of the aortic endothelium ( Hauer-Jensen, Fink & Wang, 2004 ), and enhances vascular permeability ( Hamada et al, 2020 ). However, the role the immune system plays in damaging the blood supply is rarely considered.…”

Radiation exposure of the base of the heart accelerates coronary atherosclerosis

“…Clinical studies have shown that patients receiving thoracic RT have an increased risk of coronary artery disease, valvular heart disease, congestive heart failure, pericardial disease and sudden death [17] and experimental studies have shown pre-lesion changes in the descending thoracic aorta of wild-type mice after total body irradiation (TBI, single acute exposure of 5Gy) [44]. It has been suggested that changes observed in the thoracic aorta following TBI could result not only from direct effects to the thoracic aorta but also from effects from various adjacent organs/tissues [44].…”