{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:58:47Z","timestamp":1785430727300,"version":"3.56.0"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00351"],"award-info":[{"award-number":["25-25-00351"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"award":["25-25-00351"],"award-info":[{"award-number":["25-25-00351"]}],"id":[{"id":"https:\/\/ror.org\/03y2gwe85","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Familial hypercholesterolemia (FH) is a common hereditary dyslipidemia characterized by high levels of low-density lipoprotein (LDL) cholesterol and a risk of premature atherosclerosis. Previous studies showed that cardiovascular risks persist in FH even after hypolipidemic therapy is started and are linked to a proinflammatory status of circulating monocytes. In the current study we aimed to identify FH-specific gene expression patterns of monocyte-derived M1-like macrophages in response to lipid accumulation. RNAseq was performed for four patient and four control paired samples of M1-like macrophages before and after incubation with oxidized LDL (oxLDL). A validation step was performed in 10 patients and 10 controls using real-time PCR and ELISA. RNAseq data analysis revealed 22 DEGs between FH patients and the control group before and 47 DEGs after incubation with oxLDL. Pathway enrichment analysis suggested dysregulation of inflammatory pathways especially IL-1 and chemokine signaling in response to lipid accumulation in FH M1-like macrophages. Validation experiments demonstrated increased interleukin-1\u03b2 secretion by lipid-laden M1-like macrophages in FH patients and reduced TMEM176A and TMEM176B gene expression compared to controls. Our results suggest FH M1-like macrophages may be predisposed to an accelerated immune response via interleukin-1\u03b2 due to reduced TMEM176A\/B activity.<\/jats:p>","DOI":"10.3390\/cimb48080769","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:13:47Z","timestamp":1785320027000},"page":"769","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid-Laden M1-like Macrophages of Familial Hypercholesterolemia Patients Are Characterized by Increased Interleukin-1\u03b2 Secretion and Reduced TMEM176A and TMEM176B Gene Expression"],"prefix":"10.3390","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2919-1878","authenticated-orcid":false,"given":"Artem","family":"Izyumchenko","sequence":"first","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5132-2283","authenticated-orcid":false,"given":"Tatiana","family":"Usenko","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Dracheva","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Legostaeva","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Pavlov First Saint Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3046-372X","authenticated-orcid":false,"given":"Soreiia","family":"Urazgildeeva","sequence":"additional","affiliation":[{"name":"Saint-Petersburg Medical and Social Institute, 195271 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kseniia","family":"Tanayants","sequence":"additional","affiliation":[{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Grunina","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8413-1412","authenticated-orcid":false,"given":"Ekaterina","family":"Larionova","sequence":"additional","affiliation":[{"name":"Federal State Budgetary Research Institution \u201cInstitute of Experimental Medicine\u201d, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7015-1208","authenticated-orcid":false,"given":"Pavel","family":"Suchko","sequence":"additional","affiliation":[{"name":"Centre for Genomic Technologies Cerbalab, 199106 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0091-2224","authenticated-orcid":false,"given":"Oleg","family":"Glotov","sequence":"additional","affiliation":[{"name":"Centre for Genomic Technologies Cerbalab, 199106 Saint-Petersburg, Russia"},{"name":"Pediatric Research and Clinical Center for Infectious Diseases Under the Federal Medical Biological Agency, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandr","family":"Kulikov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Diseases, Pavlov First Saint Petersburg State Medical University, 197022 Saint-Petersburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7431-6014","authenticated-orcid":false,"given":"Sofya","family":"Pchelina","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3160-2314","authenticated-orcid":false,"given":"Valentina","family":"Miroshnikova","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetic and Nanobiological Technologies, Pavlov First Saint-Petersburg State Medical University, 197022 Saint-Petersburg, Russia"},{"name":"Petersburg Nuclear Physics Institute Named by B.P. Konstantinov of National Research Centre \u00abKurchatov Institute\u00bb, 188300 Gatchina, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1002\/iub.2179","article-title":"The atherogenic role of immune cells in familial hypercholesterolemia","volume":"72","author":"Taghizadeh","year":"2020","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.athplu.2025.09.002","article-title":"Monocytes from people with Familial Hypercholesterolaemia are inflammatory, despite statin-treatment","volume":"10","author":"Williams","year":"2025","journal-title":"Atheroscler. 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