Functional analysis of gene-gene interaction networks of miR-143-3p and miR-181b-5p as regulators of coronary atherosclerotic plaque vulnerability

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Abstract

Aim. To perform functional analysis of the gene-gene interaction networks of miR-143-3p and miR-181b-5p to identify key target genes involved in regulating the coronary atherosclerotic plaque vulnerability and to identify potential therapeutic targets.

Material and methods. The study is based on the analysis of a database of 62 patients with suspected coronary artery atherosclerosis examined by multi-slice computed tomography coronary angiography. The sample included 22 patients with vulnerable plaques, 23 with stable plaques, and 17 without atherosclerosis. Analysis of circulating microRNA levels in blood plasma was performed via real-time reverse transcription polymerase chain reaction using TaqMan kits. Data on experimentally validated target genes were obtained from the TarBase v9.0 database, and data on gene interactions were obtained from the STRING v12.0 database. Interaction networks were built using CytoScape software.

Results. Analysis of the functional connections of miR-143-3p revealed an effect on the key genes HNF4A, SMAD3 and AKT1 involved in the regulation of lipid metabolism, proliferation and differentiation of vascular smooth muscle cells, and angiogenesis. For miR-181b-5p, the main target genes VCAM1, ARRB2, BCL2, and IGF1R were identified, which regulate the processes of monocyte adhesion, inflammation, apoptosis, and vascular stability. Network analysis demonstrated the convergence of PI3K / AKT, TGF-β / SMAD signaling pathways and cell death control mechanisms in regulation of atherosclerotic plaque stability.

Conclusion. Functional analysis revealed the key molecular targets of miR-143-3p and miR-181b-5p involved in pathogenesis of atherosclerosis. The identified microRNAs and their target genes represent promising therapeutic targets for stabilizing atherosclerotic plaques and preventing cardiovascular complications. Evaluation of the expression levels of these microRNAs in combination with imaging techniques can contribute to the development of personalized approaches to diagnosis and treatment of atherosclerosis.

About the authors

D. Yu. Shchekochikhin

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: rozhkov_a_n@staff.sechenov.ru
ORCID iD: 0000-0002-8209-2791
Russian Federation, Build. 2, 8 Trubetskaya St., Moscow 119048

Andrey N. Rozhkov

Institute of Personalized Cardiology of the “Digital Biodesign and Personalized Healthcare” Center, Science and Technology Park of I. M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Author for correspondence.
Email: rozhkov_a_n@staff.sechenov.ru
ORCID iD: 0000-0002-2735-076X
Russian Federation, Build. 1, 6 Bol’shaya Pirogovskaya St., Moscow 119435

N. A. Ershova

Institute of Personalized Cardiology of the “Digital Biodesign and Personalized Healthcare” Center, Science and Technology Park of I. M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: rozhkov_a_n@staff.sechenov.ru
ORCID iD: 0009-0007-6667-1287
Russian Federation, Build. 1, 6 Bol’shaya Pirogovskaya St., Moscow 119435

F. Yu. Kopylov

I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University); Institute of Personalized Cardiology of the “Digital Biodesign and Personalized Healthcare” Center, Science and Technology Park of I. M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University)

Email: rozhkov_a_n@staff.sechenov.ru
ORCID iD: 0000-0001-5124-6383
Russian Federation, Build. 2, 8 Trubetskaya St., Moscow 119048; Build. 1, 6 Bol’shaya Pirogovskaya St., Moscow 119435

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Copyright (c) 2026 Shchekochikhin D.Y., Rozhkov A.N., Ershova N.A., Kopylov F.Y.

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