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Macrophage EHD1 promotes inflammation and stabilizes sortilin to accelerate atherosclerosis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE319030 | GEO | 2026/04/28

REPOSITORIES: GEO

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Macrophage EHD1 promotes inflammation and stabilizes sortilin to accelerate atherosclerosis [scRNA-Seq]

Project description:Macrophages are the key players in the pathogenesis of atherosclerosis. Here we explored the role of the endocytic regulator EHD1 in immune responses in macrophages and determined its contribution to atherosclerosis progression. EHD1 expression profile in mouse and human plaques were determined by single cell-RNA sequencing (sc-RNA-seq) and immunofluorescence staining. Bone marrow transplantation (BMT) by transplanting bone marrow cells from Ehd1−/− or littermate wild-type mice to irradiated Ldlr−/− mice was performed to determine the effect of EHD1 deletion on atherosclerosis progression. In vitro mechanistic studies including inflammation signaling and endocytosis assays were performed in bone marrow-derived macrophages. EHD1 expression in macrophages is enhanced as atherosclerosis progresses in both mice and humans. Sc-RNA seq of aortic CD45+ cells demonstrated that EHD1 deletion attenuates pro-inflammatory responses and cell-cell interactions. Mechanistic studies revealed that EHD1 accelerates the endocytic recycling of TNFR2 and activates NF-kB, leading to increased expression of inflammatory cytokines. Moreover, EHD1 interacts with retromer and stabilizes sortilin, a retrograde cargo of retromer and a risk factor for atherosclerosis. Our study reveals novel roles for EHD1-mediated membrane trafficking in macrophage function and paves the way to innovative therapeutic strategies aiming at addressing dysregulated membrane trafficking in atherosclerosis.

2026-04-28 | GSE319029 | GEO

Macrophage EHD1 promotes inflammation and stabilizes sortilin to accelerate atherosclerosis [RNA-Seq]

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