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

Eur J Med Res. 2025 Feb 25;30(1):138. doi: 10.1186/s40001-025-02398-6.

Abstract

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).

Keywords: Endothelial function; Low-density lipoprotein cholesterol; MiRNA; Myocardial infarction; PCSK9 inhibitors.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Anticholesteremic Agents / therapeutic use
  • Carotid Intima-Media Thickness
  • Cholesterol, LDL / blood
  • Female
  • Humans
  • Male
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Middle Aged
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / genetics
  • PCSK9 Inhibitors*
  • Proprotein Convertase 9 / genetics
  • Proprotein Convertase 9 / metabolism

Substances

  • MicroRNAs
  • PCSK9 protein, human
  • PCSK9 Inhibitors
  • Proprotein Convertase 9
  • Cholesterol, LDL
  • alirocumab
  • evolocumab
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents

Associated data

  • ClinicalTrials.gov/NCT04613167