Propionate Alleviates Abdominal Aortic Aneurysm by Modulating Colonic Regulatory T-Cell Expansion and Recirculation

Fen Yang; Ni Xia; Shuang Guo; Jiyu Zhang; Yuhan Liao; Tingting Tang; Shaofang Nie; Min Zhang; Bingjie Lv; Yuzhi Lu; Jiao Jiao; Jingyong Li; Weimin Wang; Desheng Hu; Xiang Cheng

doi:10.1016/j.jacbts.2022.05.001

Propionate Alleviates Abdominal Aortic Aneurysm by Modulating Colonic Regulatory T-Cell Expansion and Recirculation

JACC Basic Transl Sci. 2022 Aug 31;7(9):934-947. doi: 10.1016/j.jacbts.2022.05.001. eCollection 2022 Sep.

Authors

Fen Yang¹, Ni Xia¹, Shuang Guo¹, Jiyu Zhang¹, Yuhan Liao¹, Tingting Tang¹, Shaofang Nie¹, Min Zhang¹, Bingjie Lv¹, Yuzhi Lu¹, Jiao Jiao¹, Jingyong Li¹, Weimin Wang², Desheng Hu³, Xiang Cheng¹

Affiliations

¹ Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, China.
² Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract

Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.

Keywords: AAA, abdominal aortic aneurysm; ANOVA, analysis of variance; CCR, C-C chemokine receptor; DEREG, depletion of regulatory T cell; DT, diphtheria toxin; EVG, Elastica van Gieson; IgG, immunoglobulin G; MMP, matrix metalloproteinase; PBS, phosphate-buffered saline; SCFA, short-chain fatty acid; SI-LP, small intestinal lamina propria; SPF, specific pathogen-free; Treg, regulatory T cell; abdominal aortic aneurysm; cLP, colonic lamina propria; colonic regulatory T cell; dLN, draining lymph node; phC, photoconversion; propionate; recirculation; short-chain fatty acids.