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.
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.