Theranostics 2022; 12(2):910-928. doi:10.7150/thno.66059 This issue

Research Paper

Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection

Yinan Chen1,2,3*, Tao Zhang4*, Fang Yao1,2,3*, Xiang Gao5, Dandan Li2, Shufang Fu2, Lin Mao2, Fei Liu2, Xuelin Zhang2, Yongle Xu6, Jianqing Deng6, Weihao Li4, Guangpu Fan7, Cangsong Xiao8, Yu Chen7, Li Wang1,2,3✉, Wei Guo6✉, Bingying Zhou1,2,3✉

1. Shenzhen Key Laboratory of Cardiovascular Disease, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen, 518057, China.
2. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
3. Key Laboratory of Pluripotent Stem Cells in Cardiac Repair and Regeneration, Chinese Academy of Medical Sciences, Beijing, 100037, China.
4. Vascular Surgery Department, Peking University People's Hospital, Beijing, 100044, China.
5. Department of Vascular Surgery, The Second Hosipital of HeBei Medical University, Shijiazhuang, 050000, China.
6. Vascular Surgery Department, The first medical Center of PLA General Hospital, Beijing, 100853, China.
7. Cardiac Surgery Department, Peking University People's Hospital, Beijing, 100044, China.
8. Cardiovascular Surgery Department, The first medical Center of PLA General Hospital, Beijing, 100853, China.
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Chen Y, Zhang T, Yao F, Gao X, Li D, Fu S, Mao L, Liu F, Zhang X, Xu Y, Deng J, Li W, Fan G, Xiao C, Chen Y, Wang L, Guo W, Zhou B. Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection. Theranostics 2022; 12(2):910-928. doi:10.7150/thno.66059. Available from https://www.thno.org/v12p0910.htm

File import instruction

Abstract

Graphic abstract

Rationale: While cell-cell interaction plays a critical role in physiology and disease, a comprehensive understanding of its dynamics in vascular homeostasis and diseases is yet absent.

Methods: Here, by use of single-cell RNA-sequencing and multi-color staining, we delineate the cellular composition and spatial characterization of human aorta with or without aortic dissection (AD).

Results: Scrutinization of cell subtype alterations revealed significantly changed fibroblast (FB)-smooth muscle cell (SMC) interactions in AD. Of these cellular interactions, LOXhigh fibroblast (fibroblast subtype 2, FB2) in diseased state exerted the most pronounced effects on pathological deterioration of SMCs in AD. In addition, pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. Finally, COL5A1 (collagen type V alpha 1 chain), one of the secreted proteins released from FB2, was significantly higher in the plasma of AD patients than in control patients, suggesting its potential use as a biomarker for AD diagnosis.

Conclusions: Our work not only identified a pivotal role of a specific FB subtype in AD progression, but also shed light on cell interaction dynamics in vascular diseases.

Keywords: aortic dissection, single-cell RNA-sequencing, cell-cell interaction, fibroblasts, BMP signaling pathway