Abstract
Radiation exposure may increase cardiovascular disease risks; however, the precise molecular/cellular mechanisms remain unclear. In the present study, we examined the hypothesis that radiation impairs cardiac stem cells (CSCs), thereby contributing to future cardiovascular disease risks. Adult C57BL/6 mice were exposed to 3 Gy γ-rays, and heart tissues were collected 24 hours later for further experiments. Although c-kit-positive cells were rarely found, radiation exposure significantly induced apoptosis and DNA damage in the cells of the heart. The ex vivo expansion of CSCs from freshly harvested atrial tissues showed a significantly lower production of CSCs in irradiated mice compared with healthy mice. The proliferative activity of CSCs evaluated by Ki-67 expression was not significantly different between the groups. However, compared to the healthy control, CSCs expanded from irradiated mice showed significantly lower telomerase activity, more 53BP1 foci in the nuclei, lower expression of c-kit and higher expression of CD90. Furthermore, CSCs expanded from irradiated mice had significantly poorer potency in the production of insulin-like growth factor-1. Our data suggest that radiation exposure significantly decreases the quantity and quality of CSCs, which may serve as sensitive bio-parameters for predicting future cardiovascular disease risks.
Highlights
The heart is generally considered to be a radioresistant organ due to its composition of postmitotic cardiac myocytes and the extremely low proliferative activity of its endothelial cells and connective tissue cells
We found that whole-body exposure of adult mice to 3 Gy γ-rays significantly induced apoptosis and DNA damage in the heart sections (P
Double staining was further performed to confirm the localization of DNA damage, which occurred in the c-kit-positive stem cells, cardiomyocytes, or other tissue cells
Summary
The heart is generally considered to be a radioresistant organ due to its composition of postmitotic cardiac myocytes and the extremely low proliferative activity of its endothelial cells and connective tissue cells. A cohort study among atomic bomb survivors in Hiroshima and Nagasaki indicated that radiation exposure over 0.5 Gy significantly elevated the risks of both stroke and heart disease [1]. Experimental studies in ApoE(-/-) mice have further demonstrated that ionizing radiation accelerates. Radiation-Induced Injuries of Cardiac Stem Cells atherosclerosis of the coronary arteries by inducing inflammation and damaging the microvascular and endocardial cells [4,5]. The molecular and cellular mechanisms of radiation-induced cardiovascular disease risks have not yet been fully elucidated because of the lack of experimental models/approaches for evaluation of these mechanisms [6,7,8]
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