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

Levstek, Tina (author), Karun, Tina (author), Rehberger Likozar, Andreja (author), Šebeštjen, Miran (author), Trebušak Podkrajšek, Katarina (author)

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.

• Language: English
• Keywords: cardiovascular disease, PCSK9, microRNA, lipoprotein(a), PCSK9 inhibitors, lipid parameters, biomarker
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 13 str.
• Numbering: Vol. 14, iss. 3, art. 632
• PID: 20.500.12556/RUL-187084
• UDC: 616.1
• ISSN on article: 2073-4425
• DOI: 10.3390/genes14030632
• COBISS.SI-ID: 144230147
• Publication date in RUL: 09.09.2026

Record is a part of a journal

• Title: Genes
• Shortened title: Genes
• Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
• ISSN: 2073-4425
• COBISS.SI-ID: 523100185

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: kardiovaskularna bolezen, PCSK9, mikroRNA, lipoprotein(a), inhibitorji PCSK9, lipidni parametri, označevalec