20.500.12556/DiRROS-32343 Interplay between microRNAs, serum proprotein convertase subtilisin/kexin type 9 (PCSK9), and lipid parameters in patients with very high lipoprotein(a) treated with PCSK9 inhibitors Proprotein convertase subtilisin/kexin type 9 (PCSK9) has an important function in the regulation of lipid metabolism. PCSK9 reduces hepatic low-density lipoprotein receptors, thereby increasing low-density lipoprotein cholesterol levels. However, its regulation remains to be elucidated, including post-transcriptional regulation by microRNAs (miRNAs). We aimed to explore the interplay between miRNAs, total serum PCSK9, and lipids during treatment with PCSK9 inhibitors. A total of 64 patients with stable coronary artery disease and very high lipoprotein(a) levels and 16 sex- and age-matched control subjects were enrolled. Patients received a PCSK9 inhibitor (evolocumab or alirocumab). Total serum PCSK9 levels were measured by immunoassay. RNA was isolated from plasma using magnetic beads, and expression of selected miRNAs was analyzed by quantitative PCR. Total serum PCSK9 levels were significantly higher in control subjects compared with patients. After 6 months of treatment with PCSK9 inhibitors, total serum PCSK9 levels increased significantly. The expression of miR-191-5p was significantly lower, and the expression of miR-224-5p and miR-483-5p was significantly higher in patients compared with control subjects. Using linear regression, the expression of miR-483-5p significantly predicted the serum PCSK9 level at baseline. After the 6-month period of therapy, the expression of miR-191-5p and miR-483-5p significantly increased. Our results support a role for miR-483-5p in regulating circulating PCSK9 in vivo. The difference in expression of miR-191-5p, miR-224-5p, and miR-337-3p between patients and control subjects suggests their possible role in the pathogenesis of coronary artery disease. cardiovascular disease PCSK9 microRNA lipoprotein(a) PCSK9 inhibitors lipid parameters biomarker kardiovaskularna bolezen PCSK9 mikroRNA lipoprotein(a) inhibitorji PCSK9 lipidni parametri označevalec true false true Angleški jezik Slovenski jezik Neznano 2026-09-07 14:33:10 2026-09-07 14:33:11 2026-09-08 04:27:07 0000-00-00 00:00:00 2023 0 0 Nasl. z nasl. zaslona; Opis vira z dne 7. 3. 2023; 1-13 str. iss. 3, [article no.] 632 Vol. 14 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.1 2073-4425 10.3390/genes14030632 144230147 RAZ_Levstek_Tina_2023.pdf RAZ_Levstek_Tina_2023.pdf 1 0BDFB3185B9E7492ED7798735E2C4621 b82b54126aa390f09f9662086b45b10986326321bf0274e4984bf1b2418dd23d 8924a43d-aab8-11f1-9d90-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=50570 https://www.mdpi.com/2073-4425/14/3/632 1 57a8944a-aab8-11f1-9d90-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=50569 Univerzitetni klinični center Ljubljana 0 0 0