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The main causes of these diseases are lipid accumulation and inflammation in large arteries. In this study, we investigated whether opioid receptor blockade impacts factors involved in atherosclerosis development. We administered naloxone to 8-week-old and 36-week-old ApoE\u2212\/\u2212 mice, then examined the expression of Col1a1, and Col3a1 in the aorta, as well as the influence of naloxone administration on aortic collagen layer thickness and proteomic changes in the aorta. Additionally, we assessed the impact of naloxone on the splenic T-cell populations. The results showed that Col3a1 expression decreased in young mice but increased in older mice. In 36-week-old mice, naloxone administration led to an increase in aortic collagen layer thickness, but remained unchanged in young mice. Proteomic analysis identified 587 proteins that were altered following naloxone treatment. Our studies suggest that the opioid system is an important factor in atherosclerosis development.<\/jats:p>","DOI":"10.3390\/cells14191559","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T12:04:52Z","timestamp":1759925092000},"page":"1559","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Opioid System Antagonism Alters Vascular Proteome and Collagen Deposition in ApoE\u2212\/\u2212 Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Kinga","family":"Jasku\u0142a","sequence":"first","affiliation":[{"name":"Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2806-6194","authenticated-orcid":false,"given":"Agata","family":"Nawrocka","sequence":"additional","affiliation":[{"name":"Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1321-2235","authenticated-orcid":false,"given":"Piotr","family":"Pozna\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Nutrigenomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-7065","authenticated-orcid":false,"given":"Aneta","family":"Stachowicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzena","family":"\u0141azarczyk","sequence":"additional","affiliation":[{"name":"Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariusz","family":"Sacharczuk","sequence":"additional","affiliation":[{"name":"Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Jastrz\u0119biec, Poland"},{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Warsaw Medical University, Banacha 1, 02-697 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5910-2955","authenticated-orcid":false,"given":"Dominik S.","family":"Skiba","sequence":"additional","affiliation":[{"name":"Department of Experimental Genomics, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, Post\u0119pu 36A, 05-552 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: Recent developments","volume":"185","author":"Lusis","year":"2022","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1161\/hc0902.104353","article-title":"Inflammation and Atherosclerosis","volume":"105","author":"Libby","year":"2002","journal-title":"Circulation"},{"key":"ref_3","first-page":"927","article-title":"Atherosclerosis: Process, Indicators, Risk Factors and New Hopes","volume":"5","author":"Setorki","year":"2014","journal-title":"Int. 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