Abstract
Background: Vascular calcification (VC) is an important predictor of prognosis in atherosclerosis, the phenotypic transformation of vascular smooth muscle cells (VSMCs) is thought to be a process of VC. However, the implications and potential mechanisms for VSMCs phenotypic transition remain unknown.Methods: To study the transformation of vascular smooth muscle cells (VSMCs) in the calcification early period, we analyzed single-cell sequencing data from carotid artery calcified core and paracellular tissue, based on the results of enrichment analysis and protein-protein interaction analysis. Upstream transcription factors were tracked and finally the results were validated using the MESA database.Results: We successfully identified a subpopulation of inflammatory macrophage-like VSMCs and determined that MMP9 is an important factor in the phenotypic transformation of VSMCs. We found that RELA regulates MMP9 expression and that knockdown of RELA attenuated MMP9 expression and reduced the expression of BMP2 and the macrophage marker LGALS3 in vascular smooth muscle in inflammatory states, while serum levels of MMP9 correlated significantly with the inflammatory response.Conclusion: This study reveals that the phenotypic transformation of VSMCs can be regulated by modulating MMP9, providing a new idea for the early treatment of VC.
Highlights
Vascular calcification (VC) is an independent predictor for the prognosis in atherosclerotic patients
Principal component analysis (PCA) was performed on the tissue cells to identify available principal components (PCs) that were subsequently used to screen for relevant genes
Our study shows that macrophage-like cells transformed from vascular smooth muscle cells (VSMCs) are involved in VC progression and that these cells are mainly associated with inflammatory responses
Summary
Vascular calcification (VC) is an independent predictor for the prognosis in atherosclerotic patients. Vascular smooth muscle cells (VSMCs) play an important role in the process of arterial VC [3]. It has been previously shown that VSMCs. Single-Cell Analysis of Vascular Calcification phenotypic transdifferentiation from contractile to osteogenic is a prerequisite for VC [4, 5] in the atherosclerotic setting, VSMCs undergo phenotypic modulation can develop into inflammatory macrophage-like cells with upregulated expression of LGALS3, or become ’synthetic’ VSMCs [6]. The use of single-cell sequencing to study the phenotypic transition of VSMCs in the calcification process has not been reported. Vascular calcification (VC) is an important predictor of prognosis in atherosclerosis, the phenotypic transformation of vascular smooth muscle cells (VSMCs) is thought to be a process of VC. The implications and potential mechanisms for VSMCs phenotypic transition remain unknown
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