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

Shinichi Ashida; Aika Yamawaki-Ogata; Masayoshi Tokoro; Masato Mutsuga; Akihiko Usui; Yuji Narita

doi:10.1038/s41598-023-27412-x

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

Sci Rep. 2023 Jan 25;13(1):1380. doi: 10.1038/s41598-023-27412-x.

Authors

Shinichi Ashida^#¹, Aika Yamawaki-Ogata^#¹, Masayoshi Tokoro¹, Masato Mutsuga¹, Akihiko Usui¹, Yuji Narita²

Affiliations

¹ Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
² Department of Cardiac Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. ynarita@med.nagoya-u.ac.jp.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin II / metabolism
Animals
Anti-Inflammatory Agents / metabolism
Aortic Aneurysm* / chemically induced
Aortic Aneurysm* / drug therapy
Aortic Aneurysm* / metabolism
Disease Models, Animal
Macrophages* / metabolism
Mice
Mice, Inbred C57BL
Tumor Necrosis Factor-alpha / metabolism

Substances

Angiotensin II
Anti-Inflammatory Agents
Tumor Necrosis Factor-alpha