2. Academic Validation
  3. Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection

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

  • Theranostics. 2022 Jan 1;12(2):910-928. doi: 10.7150/thno.66059.
Yinan Chen 1 2 3,  Tao Zhang 4,  Fang Yao 1 2 3,  Xiang Gao 5,  Dandan Li 2,  Shufang Fu 2,  Lin Mao 2,  Fei Liu 2,  Xuelin Zhang 2,  Yongle Xu 6,  Jianqing Deng 6,  Weihao Li 4,  Guangpu Fan 7,  Cangsong Xiao 8,  Yu Chen 7,  Li Wang 1 2 3,  Wei Guo 6,  Bingying Zhou 1 2 3
Affiliations

Affiliations

  • 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.
PMID: 34976220 DOI: 10.7150/thno.66059
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

BMP signaling pathway; aortic dissection; cell-cell interaction; fibroblasts; single-cell RNA-sequencing.

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