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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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>This study identified a marked upregulation of PPP2CB expression in peripheral blood leukocytes of AS patients, artery plaque of ApoE<jats:sup>\u2212\/\u2212<\/jats:sup> 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12944-025-02647-x","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T03:28:00Z","timestamp":1751513280000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["PPP2CB aggravates atherosclerosis-related dyslipidemia via LOX-1\/MAPK\/ERK signaling pathway"],"prefix":"10.1186","volume":"24","author":[{"given":"He","family":"An","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-liang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-ru","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-dong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-hua","family":"Ruan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-yan","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,3]]},"reference":[{"issue":"10159","key":"2647_CR1","doi-asserted-by":"publisher","first-page":"1736","DOI":"10.1016\/S0140-6736(18)32203-7","volume":"392","author":"Collaborators GBDCoD","year":"2018","unstructured":"Collaborators GBDCoD. 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Written informed consent was obtained from all participants prior to enrollment. The animal experiments were approved by the Animal Care and Use Committee of Hubei University of Medicine.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"229"}}