Effect of Caesium-137 chronic low dose exposure on neovascularization

Abstract

International audienceBackgroundNeovascularization is crucial for tissue irrigation adaptation in response to pathological conditions such as ischemia. This process consists of the formation of new blood vessels either by angiogenesis or by vasculogenesis. Recent studies reported that acute exposure to low doses of ionising radiation, induces an increase of angiogenesis and vasculogenesis (Ministro A, 2016; Lerman O, 2017). Furthermore, nitric oxide is stimulated in these conditions. However, effects of chronic low dose radioelements, particularly Caesium-(Cs)137, one of the most released in the environment; on neovascularization has so far not been investigated. AimWe investigated the effect of chronic low dose contamination with Cs on NO-dependent neovascularization. MethodsC57BL/6 mice received 20KB/L, 100KB/L Cs or vehicle for 6 months in drinking water. 3 other groups received the same treatment, with addition of 500µg/mL L-NAME(LN), a NO synthase blocker. We evaluated angiogenesis with aortic rings sprouting . Moreover unilateral hindlimb femoral artery ligation was performed induce surgical ischemia. Cutaneous blood flow of the ischemic and non-ischemic limb was measured with Laser Doppler Imaging and capillary density was assessed by immunohistochemistry on hindlimb muscles. Vasculogenesis was assessed by measuring the capacity of bone marrow cells differentiation into EPCs and their ability to form tubular structures in vivo in matrigel after subcutaneous injection of SDF-1 in control or mice treated with CsLN. Results/conclusionsOur preliminary results indicated a dose-dependent increase of ischemic/non-ischemic blood flow ratio in Cs-treated mice, as compared to controls. An increased blood flow ratio was also observed in Cs20KB/L -treated as compared to control/LN-treated group. A reduction of blood flow was observed in Cs100KB/L - vs Cs100KB/LN-treated group. These results suggest a dose-dependent stimulation of post-ischemic neovascularization after Cs contamination. Reduction of stimulation in Cs100KB/LN -treated group may be due to LN