{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:50:33Z","timestamp":1789588233557,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation of the Republic of Serbia","award":["451-03-33\/2026-03\/200007"],"award-info":[{"award-number":["451-03-33\/2026-03\/200007"]}]},{"award":["451-03-33\/2026-03\/200007"],"award-info":[{"award-number":["451-03-33\/2026-03\/200007"]}],"id":[{"id":"https:\/\/ror.org\/01znas443","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Faculty of Medicine Fo\u010da","award":["UIS\/MFF: 2.24-25"],"award-info":[{"award-number":["UIS\/MFF: 2.24-25"]}]},{"name":"Faculty of Medicine Fo\u010da","award":["01-3-36"],"award-info":[{"award-number":["01-3-36"]}]},{"name":"Faculty of Medicine Fo\u010da","award":["01-3-353"],"award-info":[{"award-number":["01-3-353"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Atherosclerosis is a progressive vascular disease characterized by lipid-rich plaque accumulation, oxidative stress, and chronic inflammation, contributing to coronary heart disease, stroke, and peripheral arterial disease. This study investigated the impact of inflammation, vascular calcification, and statin therapy on redox balance in blood and carotid artery plaques, aiming to identify potential biomarkers for disease assessment. Thirty-two patients undergoing carotid endarterectomy provided 34 plaque samples. Enzyme activities in plaque\/erythrocytes and \u2013SH group concentration in plasma\/plaque were measured. Pathological analysis was performed to determine inflammation\/calcification grade, the presence of mast cells and plaque composition. The results showed that mast cells were associated with reduced non-protein \u2013SH groups, indicating selective thiol consumption and serving as a qualitative marker of oxidative burden. Reduced catalase activity in erythrocytes was associated with advanced calcification, pointing to long-standing systemic oxidative stress. Statin therapy enhanced systemic superoxide-dismutase 1 activity, increased \u2013SH groups, and modulated plaque-specific glutathione reductase activity, attenuating sex-related differences in redox regulation. These findings highlight the complex interplay between systemic and local oxidative processes in atherosclerosis through alterations in redox-related biomarkers such as plasma \u2013SH group concentrations and catalase activity.<\/jats:p>","DOI":"10.3390\/ijms27125496","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:52:37Z","timestamp":1781761957000},"page":"5496","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Selective Alterations of Thiol Redox Homeostasis and Antioxidant Enzyme Activity in Advanced Atherosclerosis"],"prefix":"10.3390","volume":"27","author":[{"given":"Radmil","family":"Mari\u0107","sequence":"first","affiliation":[{"name":"Department for Vascular Surgery, University Hospital Fo\u010da, 73300 Fo\u010da, Bosnia and Herzegovina"},{"name":"Faculty of Medicine Fo\u010da, University of East Sarajevo, 73300 Fo\u010da, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branislava","family":"\u0106ur\u010di\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Fo\u010da, University of East Sarajevo, 73300 Fo\u010da, Bosnia and Herzegovina"},{"name":"Public Health Institution, Hospital Trebinje \u201cSt. Archdeacon Stefan\u20149 January\u201d, 8900 Trebinje, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-688X","authenticated-orcid":false,"given":"Teodora","family":"Vidonja Uzelac","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute for Biological Research \u201cSinisa Stankovic\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5906-3298","authenticated-orcid":false,"given":"Tanja","family":"Grahovac","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute for Biological Research \u201cSinisa Stankovic\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2772-0134","authenticated-orcid":false,"given":"Zorana","family":"Ore\u0161\u010danin Du\u0161i\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute for Biological Research \u201cSinisa Stankovic\u201d\u2014National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sr\u0111an","family":"Radanovi\u0107","sequence":"additional","affiliation":[{"name":"Department for Vascular Surgery, University Hospital Fo\u010da, 73300 Fo\u010da, Bosnia and Herzegovina"},{"name":"Faculty of Medicine Fo\u010da, University of East Sarajevo, 73300 Fo\u010da, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Batini\u0107-\u0160kipina","sequence":"additional","affiliation":[{"name":"ASA Hospital, 71000 Sarajevo, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-4352","authenticated-orcid":false,"given":"Dragana","family":"Drakul","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Fo\u010da, University of East Sarajevo, 73300 Fo\u010da, Bosnia and Herzegovina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e275","DOI":"10.1161\/CIR.0000000000001412","article-title":"2026 Heart disease and stroke statistics: A report of US and global data from the American Heart Association","volume":"153","author":"Palaniappan","year":"2026","journal-title":"Circulation"},{"key":"ref_2","unstructured":"(2026, March 24). American College of Cardiology. Available online: www.acc.org\/about-acc\/press-releases\/2025\/09\/23\/19\/19\/report-cardiovascular-diseases-caused-1-in-3-global-deaths-in-2023."},{"key":"ref_3","first-page":"e88238","article-title":"Effect of statin therapy on clinical outcomes in patients with cardiovascular risks: A systematic review and meta-analysis","volume":"17","author":"Kaur","year":"2025","journal-title":"Cureus"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"333","DOI":"10.2147\/VHRM.S17781","article-title":"Effect of atorvastatin therapy on oxidant-antioxidant status and atherosclerotic plaque formation","volume":"7","author":"Sezer","year":"2011","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1089\/ars.2013.5430","article-title":"Statins as regulators of redox state in the vascular endothelium: Beyond lipid lowering","volume":"20","author":"Margaritis","year":"2014","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1161\/hc0302.102610","article-title":"Morphological predictors of arterial remodeling in coronary atherosclerosis","volume":"105","author":"Burke","year":"2002","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1161\/hc0802.104327","article-title":"Relationship between coronary artery remodeling and plaque vulnerability","volume":"105","author":"Varnava","year":"2002","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1016\/j.bbrc.2012.06.070","article-title":"Human atherosclerotic plaque lipid extract impairs the antioxidant defense capacity of monocytes","volume":"423","author":"Etzman","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"130315","DOI":"10.1155\/2015\/130315","article-title":"The role of oxidative stress and autophagy in atherosclerosis","volume":"2015","author":"Perrotta","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Poznyak, A.V., Grechko, A.V., Orekhova, V.A., Chegodaev, Y.S., Wu, W.K., and Orekhov, A.N. (2020). Oxidative stress and antioxidants in atherosclerosis development and treatment. Biology, 9.","DOI":"10.3390\/biology9030060"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.exer.2007.06.013","article-title":"Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells","volume":"85","author":"Yang","year":"2007","journal-title":"Exp. Eye Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.ahj.2003.10.047","article-title":"Vascular smooth muscle cells and calcification in atherosclerosis","volume":"147","author":"Trion","year":"2004","journal-title":"Am. Heart J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"T\u00f3th, A., Balogh, E., and Jeney, V. (2020). Regulation of Vascular Calcification by Reactive Oxygen Species. Antioxidants, 9.","DOI":"10.3390\/antiox9100963"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"S77","DOI":"10.1097\/01.ASN.0000093240.84097.FE","article-title":"Novel cardiovascular risk factors in end-stage renal disease","volume":"15","author":"Zoccali","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101090","DOI":"10.1016\/j.arr.2020.101090","article-title":"The carotid plaque as paradigmatic case of site-specific acceleration of aging process: The microRNAs and the inflammaging contribution","volume":"61","author":"Collura","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pozo Gir\u00e1ldez, A., Bravo G\u00f3mez, A., Calmarza, P., Sienes Bailo, P., Dayaldasani Khialani, A., Montolio Breva, S., Sainz-Pastor, N., and Fort Gallifa, I. (2026). Oxidative stress and its role in vascular damage and atherosclerosis. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27021075"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Myszko, M., Bychowski, J., Skrzydlewska, E., and \u0141uczaj, W. (2025). The dual role of oxidative stress in atherosclerosis and coronary artery disease: Pathological mechanisms and diagnostic potential. Antioxidants, 14.","DOI":"10.3390\/antiox14030275"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"284","DOI":"10.2478\/jomb-2018-0041","article-title":"Superoxide dismutase isoenzymes gene expression in peripheral blood mononuclear cells in patients with coronary artery disease","volume":"38","author":"Munjas","year":"2019","journal-title":"J. Med. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1016\/j.jacc.2004.08.029","article-title":"Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: A longitudinal analysis of the PREVENT Study","volume":"44","author":"Walter","year":"2004","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.5551\/jat.43299","article-title":"Circulating oxidized low-density lipoprotein levels independently predict 10-year progression of subclinical carotid atherosclerosis: A community-based cohort study","volume":"25","author":"Gao","year":"2018","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1161\/CIRCULATIONAHA.113.002562","article-title":"Role of extracellular RNA in atherosclerotic plaque formation in mice","volume":"129","author":"Simsekyilmaz","year":"2014","journal-title":"Circulation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1159\/000087569","article-title":"Role of oxidants in mast cell activation","volume":"87","author":"Suzuki","year":"2005","journal-title":"Chem. Immunol. Allergy"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Piotin, A., Oulehri, W., Charles, A.L., Tacquard, C., Collange, O., Mertes, P.M., and Geny, B. (2024). Oxidative stress and mitochondria are involved in anaphylaxis and mast cell degranulation: A systematic review. Antioxidants, 13.","DOI":"10.3390\/antiox13080920"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1161\/HYPERTENSIONAHA.107.097386","article-title":"Endothelial function and aminothiol biomarkers of oxidative stress in healthy adults","volume":"52","author":"Ashfaq","year":"2008","journal-title":"Hypertension"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1042\/CS20180157","article-title":"Implications of plasma thiol redox in disease","volume":"132","author":"Oliveira","year":"2018","journal-title":"Clin. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"100044","DOI":"10.1016\/j.arres.2022.100044","article-title":"Emerging roles of thiol oxidoreductase-dependent mechanisms on vasomotricity regulation","volume":"6","author":"Portas","year":"2022","journal-title":"Adv. Redox Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Valerio, V., Myasoedova, V.A., Moschetta, D., Porro, B., Perrucci, G.L., Cavalca, V., Cavallotti, L., Songia, P., and Poggio, P. (2019). Impact of oxidative stress and protein S-glutathionylation in aortic valve sclerosis patients with overt atherosclerosis. J. Clin. Med., 8.","DOI":"10.3390\/jcm8040552"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15319","DOI":"10.1074\/jbc.M800021200","article-title":"Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling","volume":"283","author":"Byon","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/0167-4838(96)00043-X","article-title":"Reversible inhibition and irreversible inactivation of catalase in presence of hydrogen peroxide","volume":"1295","author":"Lardinois","year":"1996","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"12518","DOI":"10.1038\/s41598-025-97101-4","article-title":"Effects of exercise on different antioxidant enzymes and related indicators: A systematic review and meta-analysis of randomized controlled trials","volume":"15","author":"Xie","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1080\/10715760902751894","article-title":"Effect of acute vs chronic H2O2-induced oxidative stress on antioxidant enzyme activities","volume":"43","author":"Miguel","year":"2009","journal-title":"Free Radic. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.molmed.2007.11.004","article-title":"Pleiotropic effects of statin therapy: Molecular mechanisms and clinical results","volume":"14","author":"Wang","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1080\/15376520590918766","article-title":"Statins and modulation of oxidative stress","volume":"15","author":"Beltowski","year":"2005","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Allegra, A., Caserta, S., Genovese, S., Pioggia, G., and Gangemi, S. (2023). Gender differences in oxidative stress in relation to cancer susceptibility and survival. Antioxidants, 12.","DOI":"10.20944\/preprints202305.0677.v1"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kotlyarov, S. (2023). The role of smoking in the mechanisms of development of chronic obstructive pulmonary disease and atherosclerosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108725"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vidonja Uzelac, T., Tatalovi\u0107, N., Mijovi\u0107, M., Miler, M., Grahovac, T., Ore\u0161\u010danin Du\u0161i\u0107, Z., Nikoli\u0107-Koki\u0107, A., and Blagojevi\u0107, D. (2024). Ibogaine induces cardiotoxic necrosis in rats-the role of redox processes. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25126527"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Grahovac, T., Vidonja Uzelac, T., Ore\u0161\u010danin Du\u0161i\u0107, Z., Spasi\u0107, D., Mijovi\u0107, M., Nikoli\u0107-Koki\u0107, A., Miljevi\u0107, \u010c., and Blagojevi\u0107, D. (2025). Antioxidant supplementation with proclosupp protects against renal toxicity of atypical antipsychotics in rats: Implications for safer treatment strategies. Life, 15.","DOI":"10.3390\/life15111679"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3170","DOI":"10.1016\/S0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J. Biol. Chem."},{"key":"ref_39","unstructured":"Beutler, E. (1984). Red Cell Metabolism: A Manual of Biochemical Methods, Grune & Stratton."},{"key":"ref_40","first-page":"158","article-title":"Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase","volume":"70","author":"Paglia","year":"1967","journal-title":"J. Lab. Clin. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/BF01921531","article-title":"Glutathione reductase test with whole blood, a convenient procedure for the assessment of the riboflavin status in humans","volume":"30","author":"Glatzle","year":"1974","journal-title":"Experientia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"ref_43","first-page":"65","article-title":"Zur Kernntnis der blutkatalase","volume":"140","author":"Tsuchihashi","year":"1923","journal-title":"Biochem. Z."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0021-9258(18)74965-X","article-title":"Spectrophotometric studies: II. Preparations from washed blood cells; nitric oxide hemoglobin and sulfhemoglobin","volume":"112","author":"Drabkin","year":"1935","journal-title":"J. Biol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Dimic, N.D., Maric, G.D., Orescanin Dusic, Z.S., Grahovac, T.M., Vidonja Uzelac, T.F., Djuric, M.D., Nenadic, I.B., Bobos, M.M., Stevanovic, P.D., and Mihajlovic, S.J. (2025). Physiological and oxidative stress in general and spinal anesthesia for elective cesarean section in women: Is there any difference?. Life, 15.","DOI":"10.3390\/life15081158"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"Ellman","year":"1959","journal-title":"Arch. Biochem. Biophys."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5496\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T05:57:00Z","timestamp":1781762220000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/12\/5496"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,18]]},"references-count":46,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["ijms27125496"],"URL":"https:\/\/doi.org\/10.3390\/ijms27125496","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,18]]}}}