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Bone morphogenetic protein 4 (BMP4) mediates inflammation and endothelial-mesenchymal transition (EndoMT) in the vascular remodeling of angiotensin (Ang) II -induced abdominal aortic aneurysm

ABSTRACT: Abdominal aortic aneurysm (AAA) is one of the most common fatal macrovascular diseases worldwide which generates huge economic burdens on humanity. Regretfully, the pathogenesis of AAA is still not well clarified. In our study, 10×single-cell sequencing revealed that endothelial cells (ECs) dysfunction and endothelial-mesenchymal transition (EndoMT) appeared in progress of angiotensin (Ang)-II induced AAA. Three different types of ECs, including Mature ECs, EndoMT ECs and Injury & inflammation ECs successively appeared during the progression of AAA. Compared with Mature ECs, EndoMT ECs and Injury & inflammation ECs had stronger extracellular matrix synthesis function and lower metabolic level. Transcription factor analysis revealed that interferon regulatory factor 6 (Irf6) and homeobox A9 (Hoxa9) may be the critical regulons in Injury & inflammation ECs. According pseudotime trajectory and KEGG enrichment analysis, we speculated bone morphogenetic protein 4 (BMP4) regulated EndoMT, thus participating in Ang II-induced AAA. Our study represented BMP4 promotes phenotypic transition, cell migration and invasion of ECs by PI3K/AKT/mTOR pathways in vitro. Protein-protein interaction (PPI) analysis and co-immunoprecipitation (Co-IP) revealed that biglycan (BGN), a kind of small leucine-rich proteoglycan, directly combined with BMP4, which enhanced conversion degree of EndoMT. BMP4 reprogrammed ECs from anti-inflammatory to proinflammatory phenotype, which eventually led to AAA.

ORGANISM(S): Mus musculus

PROVIDER: GSE231306 | GEO | 2024/07/01

REPOSITORIES: GEO

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