Lipids Health Dis. 2025 Jul 3;24(1):229. doi: 10.1186/s12944-025-02647-x.
ABSTRACT
BACKGROUND: Dyslipidemia has been extensively documented as a key driver of cardiovascular pathology. Regulating lipid homeostasis holds promise for treating atherosclerosis (AS). Although the protein phosphatase 2 catalytic subunit beta (PPP2CB) is involved in post-transcriptional gene regulation, its role in AS-associated dyslipidemia is not well understood.
METHODS: The study included both human participants and animal models. The following techniques were employed: cell culture, extraction of exosomes, preparation of pooled hyperlipidemic serum (HS), transfection, western blotting, immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), co-immunoprecipitation, low-density lipoprotein cholesterol (LDL-C) uptake assay, biochemical assays, assessment of aortic atherosclerotic lesions, as well as statistical analysis.
RESULTS: This study identified a marked upregulation of PPP2CB expression in peripheral blood leukocytes of AS patients, artery plaque of ApoE-/- mice given a high-fat diet, and hepatic cells exposed to hyperlipidemic stimuli. Overexpression of PPP2CB in hepatic cells exacerbated lipid accumulation and low-density lipoprotein uptake, whereas silencing PPP2CB mitigated this effect. Immunofluorescence co-localization and co-immunoprecipitation analysis confirmed a direct interaction between PPP2CB and lectin-like oxidized LDL receptor-1 (LOX-1). Notably, PPP2CB manipulation disrupted hyperlipidemia-induced LOX-1 expression. Additionally, PPP2CB-mediated lipid dysregulation was linked to the activation of the LOX-1/ mitogen-activated protein kinase (MAPK)/ extracellular signal-regulated kinase (ERK) signaling cascade.
CONCLUSIONS: These results unveil PPP2CB as a novel lipid regulator in the progression of pathological AS and highlight its involvement in signaling regulation during abnormal lipid metabolism. PPP2CB could be considered a promising candidate for biomarker development and therapeutic intervention in AS.
PMID:40611318 | DOI:10.1186/s12944-025-02647-x
