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

Goran Riazi; Chloe Brizais; Imene Garali; Rida Al-Rifai; Helene Quelquejay; Virginie Monceau; Guillaume Vares; Lea Ould-Boukhitine; Damien Aubeleau; Florian Gilain; Celine Gloaguen; Morgane Dos Santos; Hafid Ait-Oufella; Teni Ebrahimian

doi:10.1371/journal.pone.0308273

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

PLoS One. 2024 Aug 1;19(8):e0308273. doi: 10.1371/journal.pone.0308273. eCollection 2024.

Authors

Affiliations

¹ Experimental Radiotoxicology and Radiobiology Laboratory (LRTOX), Institute for Radiobiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France.
² Université de Paris, Inserm U970, Paris-Cardiovascular Research Center, Paris, France.
³ Accidental Exposure Radiobiology Laboratory (LRACC), Institute for Radiobiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France.
⁴ Medical Intensive Care Unit, Hôpital Saint-Antoine, AP-HP, Sorbonne Université, Paris, France.

Abstract

Background: 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.

Methods: 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.

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-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.

Conclusion: Moderate doses of ionizing radiation mitigate AAA either through VSCM phenotype or inflammation modulation, depending on the time of irradiation.

Copyright: © 2024 Riazi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

MeSH terms

Angiotensin II* / pharmacology
Animals
Aortic Aneurysm, Abdominal* / etiology
Aortic Aneurysm, Abdominal* / metabolism
Aortic Aneurysm, Abdominal* / pathology
Cell Proliferation / radiation effects
Collagen / metabolism
Disease Models, Animal
Interleukin-10 / genetics
Interleukin-10 / metabolism
Male
Mice
Muscle, Smooth, Vascular* / metabolism
Muscle, Smooth, Vascular* / pathology
Muscle, Smooth, Vascular* / radiation effects
Myocytes, Smooth Muscle* / metabolism
Myocytes, Smooth Muscle* / pathology
Myocytes, Smooth Muscle* / radiation effects
Radiation, Ionizing*

Substances

Angiotensin II
Interleukin-10
Collagen

Grants and funding

For this work we obtained a grant from Electricité de France (EDF Energy). However, the funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.