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

**Authors:** 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, Venkateswaran Subramanian, Venkateswaran Subramanian, Venkateswaran Subramanian

PMC · DOI: 10.1371/journal.pone.0308273 · 2024-08-01

## TL;DR

Moderate radiation reduces abdominal aortic aneurysm in mice, either by changing muscle cell behavior or reducing inflammation, depending on when the radiation is given.

## Contribution

The study reveals that moderate radiation can mitigate AAA through distinct mechanisms depending on irradiation timing.

## Key findings

- Radiation before AngII infusion reduces AAA by altering vascular smooth muscle cell phenotype.
- Radiation after AngII infusion reduces AAA by increasing anti-inflammatory macrophages.
- Radiation significantly reduces aortic dilation and AAA incidence in mice.

## Abstract

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.

## Linked entities

- **Proteins:** IL10 (interleukin 10)
- **Diseases:** abdominal aortic aneurysm (MONDO:0005350), AAA (MONDO:0009279)

## Full-text entities

- **Genes:** AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}
- **Diseases:** inflammation (MESH:D007249), VSCM (OMIM:155310), AAA (MESH:D017544), cardiovascular diseases (MESH:D002318)
- **Chemicals:** pomp (MESH:C045495)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11293671/full.md

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Source: https://tomesphere.com/paper/PMC11293671