Dataset Information

CEBPB drives endothelial pathological phenotype and promotes atherosclerosis by directly upregulating TGFBR1 expression [scRNA-seq]

ABSTRACT: Endothelial cell (EC) dysfunction is crucial in chronic vascular inflammation and diseases like atherosclerosis. An unknown endothelial pathological phenotype potentially driving atherosclerosis was hinted in our previous study. However, the detailed characterizations and underlying molecular mechanisms remain unclear. Here, we have defined a new endothelial pathological phenotype, characterized by high expression of fibroblast and pro-inflammatory genes with a rapid reduction in EC fate genes by performing single-cell RNA sequencing. Further analysis revealed that increased CEBPB contributes to the fibroblast and inflammatory feature of these atherogenic ECs, which was further confirmed in cultured human aortic ECs. Mechanistically, IL-1β-induced high expression of CEBPB triggers TGF-β signaling and subsequent regulation of downstream genes. This occurs through direct interaction of CEBPB with the promotor region of TGF-β receptor type I (TGFBR1), resulting in its upregulation. Furthermore, exacerbating atherosclerotic plaque area, enhanced vascular inflammation and increased endothelial TGFBR1 expression were confirmed by endothelial overexpression of CEBPB in vivo. These findings suggest endothelial CEBPB functions as a novel regulator of TGFBR1, driving endothelial pathological phenotype, promoting vascular inflammation and atherosclerosis. Targeting endothelial CEBPB may offer new therapeutic avenues for atherosclerotic diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE278346 | GEO | 2025/12/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Endothelial cells (ECs) act as gatekeepers and signalling hubs that coordinate communication between blood vessels and surrounding tissues by regulating vascular tone, immune responses and numerous other physiological processes. During vascular inflammation commonly associated with aging, atherosclerosis, diabetes and autoimmunity, a range of biological, environmental and physical stressors can induce activation and apoptosis of ECs. Apoptotic bodies (ApoBDs) are large (~1–5 μm), membrane‑bound extracellular vesicles generated solely through apoptotic cell disassembly, that are increasingly recognised as mediators of intercellular communication via the transfer of bioactive molecules to target cells. Although EC apoptosis is a central feature of vascular inflammatory disorders, the formation of EC‑derived ApoBDs and their immunomodulatory roles when formed in an inflammatory environment, remains poorly defined. This study aimed to characterise the functional properties of EC‑derived ApoBDs generated under inflammatory conditions in vitro. A proteomics analysis of EC‑derived ApoBDs revealed that EC‑ApoBDs generated during inflammation (‘iApoBDs’) were enriched in inflammatory cytokines/chemokines, adhesion molecules and antigen presentation machinery compared with non inflammatory (‘ApoBD’) controls. Functionally, iApoBDs promoted monocyte chemotaxis via the release of MCP-1, while altered expression of the adhesion molecule ICAM 1 enhanced efferocytosis by macrophages in vitro and in vivo. Furthermore, iApoBDs generated from antigen pulsed HUVECs promoted IFN‑𝛾 expression by peptide specific CD8+ T cells in an in vitro model of antigen presentation. These findings demonstrate that within an inflammatory setting, apoptotic ECs can participate in continued communication with their environment via the generation of ApoBDs, thereby modulating innate and adaptive immune processes. The formation of ApoBDs by ECs may serve as a target for therapeutic interventions in inflammatory vascular diseases.

Dataset Information

CEBPB drives endothelial pathological phenotype and promotes atherosclerosis by directly upregulating TGFBR1 expression [scRNA-seq]

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets