Effects of moderate doses of ionizing radiation on experimental abdominal aortic aneurysm

Objectives: Exposure to ionizing radiation has been linked to cardiovascular diseases. However, the impact of moderate doses of radiation on abdominal aortic aneurysm (AAA) remains unknown. Approaches : Angiotensin II-infused Apoe-/- mice were irradiated (acute, 1 Gray) either 3 days before (Day-3) or 1 day after (Day+1) pomp implantation. Primary aortic smooth muscle cells (SMCs) isolated were irradiated (acutely 1 Gray) for mechanistic studies and functional tested in vitro. Results: Day-3 and Day+1 irradiation resulted in a significant reduction in aorta dilation (Control: 1.39+/-0.12; Day-3: 1.12+/-0.11; Day+1: 1.15+/-0.08 mm, P<0.001) and AAA incidence (Control: 81.0%; Day-3: 33.3%, Day+1: 53.3%) compared to the non_x0002_irradiated group. Day-3 and Day+1 irradiation led to an increase in collagen content in the adventitia (Thickness control: 23.64+/-2.9; Day-3: 54.39+/-15.5; Day+1 37.55+/- 10.8 mm, P=0.006). However, the underlying protective mechanisms were different between Day-3 and Day+1 groups. Irradiation before Angiotensin II (AngII) infusion mainly modulated vascular smooth muscle cells (VSMCs) phenotype with a decrease in contractile profile and enhanced proliferative and migratory activity. Irradiation after AngII infusion led to an increase in macrophage content with a local anti-inflammatory phenotype characterized by the upregulation of M2-like gene and IL-10 expression. Conclusion: Moderate doses of ionizing radiation mitigates AAA either through VSCM phenotype or inflammation modulation according to the time of irradiation. Overall design: Aortas from Angiotensin II-infused Apoe-/- mice, irradiated 3 days before or 1 day after pomp implantation, were used for RNA-seq analysis.