Riazi Goran, Brizais Chloe, Garali Imene, Al-Rifai Rida, Quelquejay Helene, Monceau Virginie, Vares Guillaume, Ould-Boukhitine Lea, Aubeleau Damien, Gilain Florian, Gloaguen Celine, Dos Santos Morgane, Ait-Oufella Hafid, Ebrahimian Teni
Experimental Radiotoxicology and Radiobiology Laboratory (LRTOX), Institute for Radiobiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France.
Université de Paris, Inserm U970, Paris-Cardiovascular Research Center, Paris, France.
PLoS One. 2024 Aug 1;19(8):e0308273. doi: 10.1371/journal.pone.0308273. eCollection 2024.
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.
Angiotensin II-infused Apoe-/- mice were irradiated (acute, 1 Gray) either 3 days before (Day-3) or 1 day after (Day+1) pomp implantation. Isolated primary aortic vascular smooth muscle cells (VSMCs) were irradiated (acute 1 Gray) for mechanistic studies and functional testing in vitro.
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-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 cell (VSMC) 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.
Moderate doses of ionizing radiation mitigate AAA either through VSCM phenotype or inflammation modulation, depending on the time of irradiation.
暴露于电离辐射与心血管疾病有关。然而,中等剂量辐射对腹主动脉瘤(AAA)的影响仍不清楚。
在植入泵前3天(第-3天)或植入后1天(第+1天),对输注血管紧张素II的Apoe-/-小鼠进行照射(急性,1格雷)。分离的原代主动脉血管平滑肌细胞(VSMC)接受照射(急性1格雷),用于体外机制研究和功能测试。
与未照射组相比,第-3天和第+1天照射导致主动脉扩张显著降低(对照组:1.39±0.12;第-3天:1.12±0.11;第+1天:1.15±0.08毫米,P<0.001)和AAA发病率降低(对照组:81.0%;第-3天:33.3%,第+1天:53.3%)。第-3天和第+1天照射导致外膜胶原含量增加(厚度对照组:23.64±2.9;第-3天:54.39±15.5;第+1天37.55±10.8毫米,P = 0.006)。然而,第-3天和第+1天组的潜在保护机制不同。血管紧张素II(AngII)输注前照射主要调节血管平滑肌细胞(VSMC)表型,收缩特性降低,增殖和迁移活性增强。AngII输注后照射导致巨噬细胞含量增加,具有以M2样基因上调和IL-10表达为特征的局部抗炎表型。
中等剂量的电离辐射可通过VSCM表型或炎症调节减轻AAA,这取决于照射时间。