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Prof. Zhang Tao's Research Team Reveals Pathogenesis of Aortic Dissection from Perspective of Single Cells

2022-03-31

The research team of Prof. Zhang Tao from the Department of Vascular Surgery of Peking University People’s Hospital, the research team of Prof. Wang Li from the State Key Laboratory of Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences, and the research team of Prof. Guo Wei from the Department of Vascular Surgery of the First Medical Center of Chinese PLA General Hospital published a paper titled “Dysregulation of interaction between LOXhigh fibroblast and smooth muscle cells contributes to the pathogenesis of aortic dissection” in the journal of Theranostics (F:11.556). This research found new targets for drug treatment of aortic dissection (AD) and increased the possibility for early diagnosis and rapid triage of AD.

Aortic dissection (AD) is a life-threatening aortic disease associated with high morbidity and mortality. Prof. Zhang Tao's research group focuses on exploring cell-cell interactions and functional targets in vascular homeostasis and disease development. By us of single-cell RNA-sequencing and multi-color staining, the authors delineated the cellular composition and spatial characterization of human aorta with or without aortic dissection.

 

Through scrutinizing cell subtype alterations, the research 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. The results also showed that pharmacologically targeting the BMP (bone morphogenetic protein) signaling pathway effectively suppressed FB2 state transition and reduced AD incidence in mice. In addition, the study found that 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.

 

The study has demonstrated the feasibility of treating AD from the perspective of regulating cell-cell interactions, which not only provides a new idea for the treatment of AD in the future, but also finds a new target for the drug treatment of AD: suppressing state transition of LOXhigh fibroblast. At the same time, this study completed the screening of AD biomarkers by single-cell sequencing technology for the first time, which proved the role of single-cell sequencing technology in clinical diagnosis of AD, and also raised the possibility for early diagnosis and rapid triage of AD in the future.

 

The research was supported by the National Natural Science Foundation of China and the National Key R & D Program of China. Zhang Tao, Chen Yinan and Yao Fang are the co-first authors of the article. Wang Li, Guo Wei and Zhou Bingying are the co-corresponding authors of the article.

 

Paper link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8692905/