Chronic Exposure to External Low-Dose Gamma Radiation Induces an Increase in Anti-inflammatory and Anti-oxidative Parameters Resulting in Atherosclerotic Plaque Size Reduction in ApoE-/- Mice.

Populations living in radiation-contaminated territories, such as Chernobyl and Fukushima, are chronically exposed to external gamma radiation and internal radionuclide contamination due to the large amount of 137Cs released in the environment. The effect of chronic low-dose exposure on the development of cardiovascular diseases remains unclear. Previously reported studies have shown that low-dose radiation exposure could lead to discrepancies according to dose rate. In this study, we examined the effect of very low-dose and dose-rate chronic external exposure on atherosclerosis development. ApoE-/- mice were chronically irradiated with a gamma source for 8 months at two different dose rates, 12 and 28 µGy/h, equivalent to dose rates measured in contaminated territories, with a cumulative dose of 67 and 157 mGy, respectively. We evaluated plaque size and phenotype, inflammatory profile and oxidative stress status. The results of this study showed a decrease in plaque sizes and an increase in collagen content in ApoE-/- mice exposed to 28 µGy/h for 8 months compared to nonexposed animals. The plaque phenotype was associated with an increase in anti-inflammatory and anti-oxidative gene expression. These results suggest that chronic low-dose gamma irradiation induces an upregulation of organism defenses leading to a decrease in inflammation and plaque size. To our knowledge, this is the first study to describe the possible effect of chronic external very low-dose ionizing radiation exposure for 8 months. This work could help to identify the potential existence of a dose threshold, below that which harmful effects are not exhibited and beneficial effects are potentially observed. Furthermore, these findings permit consideration of the importance of dose rate in radiation protection.

Cell therapy based on adipose tissue-derived stromal cells promotes physiological and pathological wound healing.

OBJECTIVE: We hypothesized that adipose tissue may contain progenitors cells with cutaneous and angiogenic potential. METHODS AND RESULTS: Adipose tissue-derived stroma cells (ADSCs) were administrated to skin punched wounds of both nonirradiated and irradiated mice (20 Gy, locally). At day 14, ADSCs promoted dermal wound healing and enhanced wound closure, viscolesticity, and collagen tissue secretion in both irradiated and nonirradiated mice. Interestingly, GFP-positive ADSCs incorporated in dermal and epidermal tissue in vivo and expressed epidermal markers K5 and K14. Cultured ADSCs in keratinocyte medium have been shown to differentiate into K5- and K14-positive cells and produced high levels of KGF. At Day 7, ADSCs also improved skin blood perfusion assessed by laser Doppler imaging, capillary density, and VEGF plasma levels in both irradiated and nonirradiated animals. GFP-positive ADSCs incorporated into capillary structures in vivo and expressed the endothelial cell marker CD31. Finally, in situ interphase fluorescence hybridization showed that a small number of ADSCs have the potential to fuse with endogenous keratinocytes. CONCLUSIONS: ADSCs participate in dermal wound healing in physiological and pathological conditions by their ability to promote reepithelialization and angiogenesis. Hence, adipose lineage cells represent a new cell source for therapeutic dermal wound healing.