Treatment with PCSK9 inhibitors influences microRNAs expression and changes of arterial wall properties : a randomized controlled trial

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

Background: MicroRNAs (miRNAs) are involved in the synthesis of proprotein convertase subtilisin–kexin type 9 (PCSK9), one of the regulators of low-density lipoprotein cholesterol (LDL-C) metabolism, and are directly involved in the atherosclerotic process. The aim of this study was to verify whether treatment with PCSK9 inhibitors (PCSK9i) and changes in the expression of miRNAs involved in PCSK9 metabolism are associated with arterial wall properties in stable post-myocardial infarction (MI) patients with insufficiently regulated LDL-C levels and significantly increased Lp(a) levels. Methods: Ninety-five patients after MI were enrolled and randomized to a placebo (N = 31) or PCSK9i group (N = 64). The treatment group received subcutaneous alirocumab 150 mg or evolocumab 140 mg, every 2 weeks. Blood for biochemical and epigenetic analysis was taken and ultrasound measurements of flow-mediated dilation of brachial artery (FMD), carotid intima–media thickness (c-IMT) and pulse wave velocity (PWV) were performed initially and after 6 months of treatment. The expression of the selected 5 miRNAs (miR-191-5p, miR-224-5p, miR-337-3p, miR-483-5p, and miR-552-3p) was quantified using quantitative polymerase chain reaction. Results: A decrease in c-IMT was associated with a decrease in the expression of miR-337-3p (ρ = 0.329; p = 0.010) and miR-483-5p (ρ = 0.324; p = 0.012). We did not detect any associations between miRNA changes and FMD or PWV. Conclusions: Our results suggest that changes in the selected miRNAs are associated with changes in the morphological properties of the arterial wall. We have shown that the decrease in miR-483-5p expression present a good indicator of the regression of morphological atherosclerotic change. The trial registration: The study is registered with CinicalTrials under the number NCT04613167, date of registration November 2nd, 2020. Approval for this study was obtained from the National Medical Ethics Committee of the Republic of Slovenia (reference number: KME 0120-357/2018/8).

• Language: English
• Keywords: miRNA, endothelial function, PCSK9 inhibitors, myocardial infarction, low-density lipoprotein cholesterol
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy; MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2025
• Number of pages: 9 str.
• Numbering: Vol. 30, art. 138
• PID: 20.500.12556/RUL-168201
• UDC: 612.111:616.127-005.8
• ISSN on article: 2047-783X
• DOI: 10.1186/s40001-025-02398-6
• COBISS.SI-ID: 231157507
• Publication date in RUL: 02.04.2025

Record is a part of a journal

• Title: European journal of medical research
• Shortened title: Eur. j. med. res.
• Publisher: I. Holzapfel, BioMed Central
• ISSN: 2047-783X
• COBISS.SI-ID: 523081753

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: miRNA, endotelijska funkcija, zaviralci PCSK9, lipoprotein nizke gostote, holesterol, endotelij, miokardni infarkt