Role of smooth muscle-derived S100A4 in an atherosclerotic mouse model
نویسندگان
چکیده
Abstract Background S100A4, a small calcium binding protein, plays an important role in vascular smooth muscle cell (SMC) phenotypic switch but its implication atherosclerotic plaque development and particularly SMC plasticity is not clear yet. By neutralizing S100A4 using monoclonal antibody, we have previously shown reduction overall burden. However, this strategy did distinguish the different contribution between SMCs or other S100A4-expressing cells (e.g. macrophages). Methods Herein, used lineage tracing mouse model which induced specific deletion of (SMC-S100A4Δ/Δ) ApoE−/− background. High cholesterol diet was maintained for 12 weeks, after which, SMC-S100A4Δ/Δ control mice (SMC-S100A4wt/wt) were sacrificed aortas processed staining single RNA sequencing (scRNA-seq). Results We showed that modulated composition rather than size. ScRNA-seq analysis from SMC-S100A4wt/wt macrophages dendritic increase total SMCs, likely participating fibrous cap stabilization. populations decrease macrophage-like inflammatory phenotype fibroblast-like repair phenotype, as well retention markers, namely Acta2 Myh11. Gene expression revealed inflammation fatty acid metabolism, extracellular matrix-related genes, classical markers maintenance contractile phenotype. Conclusion report intrinsic function establishment fate within and, surprisingly, global impact on microenvironnement status. Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): Swiss Science Foundation
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Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque.
The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A...
متن کاملRole of human smooth muscle cell progenitors in atherosclerotic plaque development and composition.
AIMS We analysed the possible protective role of human endothelial (EPCs) and smooth muscle (SPCs) progenitor cells on atherosclerosis development in apoE(-/-)RAG2(-/-) mice. We determined plasma levels of SPCs in coronary patients. METHODS AND RESULTS ApoE(-/-)RAG2(-/-) mice received four intravenous injections of saline, 5 x 10(5) SPCs, or 5 x 10(5) EPCs every other week, one (preventive ap...
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ژورنال
عنوان ژورنال: European Heart Journal
سال: 2022
ISSN: ['2634-3916']
DOI: https://doi.org/10.1093/eurheartj/ehac544.3050