[PGAM5 deficiency attenuates atherosclerosis, enhances oxidized LDL uptake by liver sinusoidal endothelial cells and reshapes circulating lipidome in mice].
Year: 2026
Type: article
Abstract: OBJECTIVES: To investigate the effects of mitochondrial phosphoglycerate mutase 5 (PGAM5) deficiency on endocytic function of liver sinusoidal endothelial cells (LSECs) and circulating lipid remodeling and their association with atherosclerosis (AS). METHODS: mice fed WD after AAV-PCSK9 injection). Aortic plaques, hepatic lipid deposition, and plasma lipids were assessed by Oil Red O, HE, Masson staining, and lipid assays. Liver proteomics and single-cell RNA-seq were used to screen the pathways and analyze cell subsets. Plasma metabolomics and lipidomics screened key differential metabolites. In immortalized human LSECs (HLSECs), PGAM5 knockdown was used to assess oxidized low-density lipoprotein (oxLDL) uptake under metabolite interventions. RESULTS: mice. Plasma lipidomics showed altered lipid profiles following PGAM5 deficiency. PGAM5 knockdown enhanced oxLDL uptake by HLSECs, while AA or L-PC inhibited this process. CONCLUSIONS: PGAM5 deficiency is associated with enhanced endocytic function of LSECs and circulating lipid remodeling, which may contribute to ameliorated AS.
Source: PubMed
Language: Chinese
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223846992