{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,7]],"date-time":"2026-06-07T00:11:41Z","timestamp":1780791101782,"version":"3.54.1"},"reference-count":33,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T00:00:00Z","timestamp":1761696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["UMO-2022\/45\/N\/NZ7\/01622"],"award-info":[{"award-number":["UMO-2022\/45\/N\/NZ7\/01622"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Heterozygous familial hypercholesterolemia (HeFH) is a common autosomal dominant genetic disease (1:250) characterized by elevated LDL-C. Patients with HeFH are at increased risk of premature atherosclerosis and have at least a 10-fold greater chance of cardiovascular disease (CVD). The present study examines the effect of PCSK9 inhibitor treatment (iPCSK9: arilocumab or evolocumab) on DNA damage in HeFH patients. Fifty-six patients were studied, with a normolipidemic group (control; n = 20) and patients with HeFH (study group; n = 36). DNA damage was determined by alkaline comet assay and PCSK9 protein level by ELISA. PCSK9i treatment was found to be associated with lower DNA damage, Lp(a), PCSK9, and lipid profile compared to before treatment. However, 16 of 36 patients still had Lp(a) values above 125 nmol\/L, and reduced Lp(a) did not correlate with reduced DNA damage. Reduced PCSK9 demonstrated a moderately positive correlation (r = 0.48) with reduced DNA damage. PCSK9i therapy reduces the level of DNA damage in HeFH patients, regardless of the type of inhibitor. While our findings confirm that PCSK9 treatment can reduce DNA damage, the mechanism remains unclear.<\/jats:p>","DOI":"10.3390\/ijms262110529","type":"journal-article","created":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T17:38:22Z","timestamp":1761759502000},"page":"10529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Proprotein Convertase Subtilisin\/Kexin Type 9 (PCSK9) Inhibitor Therapy Reduces the Level of DNA Damage in Patients with Heterozygous Familial Hypercholesterolemia"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4755-425X","authenticated-orcid":false,"given":"Ewelina","family":"Wo\u017aniak","sequence":"first","affiliation":[{"name":"Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1\/5, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1\/5, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Pawlos","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1\/5, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3659-8115","authenticated-orcid":false,"given":"Marlena","family":"Broncel","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1\/5, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Sata\u0142a","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1\/5, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3044-2953","authenticated-orcid":false,"given":"Bo\u017cena","family":"Bukowska","sequence":"additional","affiliation":[{"name":"Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141\/143, 90-236 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Gorzelak-Pabi\u015b","sequence":"additional","affiliation":[{"name":"Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1\/5, 91-347 Lodz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.atherosclerosis.2018.06.855","article-title":"Epidemiology of Familial Hypercholesterolaemia: Community and Clinical","volume":"277","author":"Ray","year":"2018","journal-title":"Atherosclerosis"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s40256-024-00682-0","article-title":"Efficacy of Proprotein Convertase Subtilisin\/Kexin Type 9 Inhibitors in Patients with Heterozygous Familial Hypercholesterolemia: A Meta-Analysis","volume":"25","author":"Movahedan","year":"2025","journal-title":"Am. 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