Single-Cell RNA-Seq Reveals a Population of Smooth Muscle Cells Responsible for Atherogenesis.

Autor:	Shi X; 1School of Engineering Medicine, Beihang University, Beijing, China.; 2Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China., Zhu S; 1School of Engineering Medicine, Beihang University, Beijing, China.; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Liu M; 1School of Engineering Medicine, Beihang University, Beijing, China., Stone SS; 4Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA., Rong Y; 1School of Engineering Medicine, Beihang University, Beijing, China.; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Mao K; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Xu X; 1School of Engineering Medicine, Beihang University, Beijing, China., Ma C; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Jiang Z; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Zha Y; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Yan C; 1School of Engineering Medicine, Beihang University, Beijing, China., Yu X; 3School of Biological Science and Medical Engineering, Beihang University, Beijing, China., Wu D; 5Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China., Liu G; 2Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China., Mi J; 6Beijing SINOGENE Biotechnology Co., Ltd, Beijing, China., Zhao J; 6Beijing SINOGENE Biotechnology Co., Ltd, Beijing, China., Li Y; 6Beijing SINOGENE Biotechnology Co., Ltd, Beijing, China., Ding Y; 4Department of Neurosurgery, Wayne State University School of Medicine, Detroit, MI, USA., Wang X; 1School of Engineering Medicine, Beihang University, Beijing, China.; 7Key Laboratory of Big Data-Based Precision Medicine (Beihang University) Ministry of Industry and Information Technology, Beijing, China., Zhang YB; 1School of Engineering Medicine, Beihang University, Beijing, China.; 7Key Laboratory of Big Data-Based Precision Medicine (Beihang University) Ministry of Industry and Information Technology, Beijing, China., Ji X; 2Beijing Institute for Brain Disorders, Capital Medical University, Beijing, China.; 5Department of Neurology and China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University, Beijing, China.
Jazyk:	angličtina
Zdroj:	Aging and disease [Aging Dis] 2022 Dec 01; Vol. 13 (6), pp. 1939-1953. Date of Electronic Publication: 2022 Dec 01 (Print Publication: 2022).
DOI:	10.14336/AD.2022.0313
Abstrakt:	Understanding the regional propensity differences of atherosclerosis (AS) development is hindered by the lack of animal models suitable for the study of the disease process. In this paper, we used 3S-ASCVD dogs, an ideal large animal human-like models for AS, to interrogate the heterogeneity of AS-prone and AS-resistant arteries; and at the single-cell level, identify the dominant cells involved in AS development. Here we present data from 3S-ASCVD dogs which reliably mimic human AS pathophysiology, predilection for lesion sites, and endpoint events. Our analysis combined bulk RNA-seq with single-cell RNA-seq to depict the transcriptomic profiles and cellular atlas of AS-prone and AS-resistant arteries in 3S-ASCVD dogs. Our results revealed the integral role of smooth muscle cells (SMCs) in regional propensity for AS. Notably, TNC + SMCs were major contributors to AS development in 3S-ASCVD dogs, indicating enhanced extracellular matrix remodeling and transition to myofibroblasts during the AS process. Moreover, TNC + SMCs were also present in human AS-prone carotid plaques, suggesting a potential origin of myofibroblasts and supporting the relevance of our findings. Our study provides a promising large animal model for pre-clinical studies of ASCVD and add novel insights surrounding the regional propensity of AS development in humans, which may lead to interventions that delay or prevent lesion progression and adverse clinical events. Competing Interests: Competing interests The authors declare that they have no competing interests. (copyright: © 2022 Shi et al.)
Databáze:	MEDLINE
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