Administration of anti-inflammatory M2 macrophages suppresses progression of angiotensin II-induced aortic aneurysm in mice

• Published in: Scientific reports 2023-01, Vol.13 (1), p.1380-10, Article 1380
• Main Authors: Ashida, Shinichi, Yamawaki-Ogata, Aika, Tokoro, Masayoshi, Mutsuga, Masato, Usui, Akihiko, Narita, Yuji
• Format: Article
• Language: English
• Subjects: 692/308/2171; 692/699/75/593; Angiotensin; Angiotensin II; Angiotensin II - metabolism; Animals; Anti-Inflammatory Agents - metabolism; Aortic Aneurysm - chemically induced; Aortic Aneurysm - drug therapy; Aortic Aneurysm - metabolism; Aortic aneurysms; Apolipoprotein E; Disease Models, Animal; Extracellular matrix; Humanities and Social Sciences; Interleukin 10; Interleukin 4; Interleukin 6; Macrophages; Macrophages - metabolism; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; multidisciplinary; Science; Science (multidisciplinary); Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-27412-x

Aortic aneurysm (AA) is a vascular disorder characterized pathologically by inflammatory cell invasion and extracellular matrix (ECM) degradation. It is known that regulation of the balance between pro-inflammatory M1 macrophages (M1Ms) and anti-inflammatory M2 macrophages (M2Ms) plays a pivotal role in AA stabilization. We investigated the effects of M2M administration in an apolipoprotein E-deficient (apoE −/− ) mouse model in which AA was induced by angiotensin II (ATII) infusion. Mice received intraperitoneal administration of 1 million M2Ms 4 weeks after ATII infusion. Compared with a control group that was administered saline, the M2M group exhibited reduced AA expansion; decreased expression levels of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1); and a lower M1M/M2M ratio. Moreover, the M2M group exhibited upregulation of anti-inflammatory factors, including IL-4 and IL-10. PKH26-labeled M2Ms accounted for 6.5% of cells in the aneurysmal site and co-expressed CD206. Taken together, intraperitoneal administration of M2Ms inhibited AA expansion by reducing the inflammatory reaction via regulating the M1M/M2M ratio. This study shows that M2M administration might be useful for the treatment of AA.