Single-cell RNA sequencing reveals the cellular heterogeneity of aneurysmal infrarenal abdominal aorta

Author:

Zhao Guizhen1ORCID,Lu Haocheng1ORCID,Chang Ziyi12ORCID,Zhao Yang1ORCID,Zhu Tianqing1,Chang Lin1,Guo Yanhong1,Garcia-Barrio Minerva T1,Chen Y Eugene1,Zhang Jifeng1ORCID

Affiliation:

1. Frankel Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, NCRC Bldg26, Room 357S. 2800 Plymouth Rd, Ann Arbor, MI 48109, USA

2. Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China

Abstract

Abstract Aims The artery contains numerous cell types which contribute to multiple vascular diseases. However, the heterogeneity and cellular responses of these vascular cells during abdominal aortic aneurysm (AAA) progression have not been well characterized. Methods and results Single-cell RNA sequencing was performed on the infrarenal abdominal aortas (IAAs) from C57BL/6J mice at Days 7 and 14 post-sham or peri-adventitial elastase-induced AAA. Unbiased clustering analysis of the transcriptional profiles from >4500 aortic cells identified 17 clusters representing nine-cell lineages, encompassing vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells, immune cells (macrophages, T cells, B cells, and dendritic cells), and two types of rare cells, including neural cells and erythrocyte cells. Seurat clustering analysis identified four smooth muscle cell (SMC) subpopulations and five monocyte/macrophage subpopulations, with distinct transcriptional profiles. During AAA progression, three major SMC subpopulations were proportionally decreased, whereas the small subpopulation was increased, accompanied with down-regulation of SMC contractile markers and up-regulation of pro-inflammatory genes. Another AAA-associated cellular response is immune cell expansion, particularly monocytes/macrophages. Elastase exposure induced significant expansion and activation of aortic resident macrophages, blood-derived monocytes and inflammatory macrophages. We also identified increased blood-derived reparative macrophages expressing anti-inflammatory cytokines suggesting that resolution of inflammation and vascular repair also persist during AAA progression. Conclusion Our data identify AAA disease-relevant transcriptional signatures of vascular cells in the IAA. Furthermore, we characterize the heterogeneity and cellular responses of VSMCs and monocytes/macrophages during AAA progression, which provide insights into their function and the regulation of AAA onset and progression.

Funder

National Institutes of Health

American Heart Association

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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