The Link between miRNAs and PCKS9 in Atherosclerosis

Mirjana Macvanin; Zoran Gluvic; Aleksandra Klisic; Mia Manojlovic; Jasjit Suri; Manfredi Rizzo; Esma Isenovic

doi:10.2174/0109298673262124231102042914

The Link between miRNAs and PCKS9 in Atherosclerosis

Authors: Macvanin M.¹, Gluvic Z.², Klisic A.³, Manojlovic M.⁴, Suri J.⁵, Rizzo M.⁶, Isenovic E.⁷
Affiliations:
1. Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade
2. Department of Endocrinology and Diabetes, School of Medicine, University Clinical-Hospital Centre Zemun-Belgrade, Clinic of Internal Medicine,, University of Belgrade
3. Faculty of Medicine, Center for Laboratory Diagnostic, Primary Health Care Center, University of Montenegro- Faculty of Medicine
4. Faculty of Medicine Novi Sad,, University of Novi Sad
5. Stroke Monitoring and Diagnostic Division Monitoring and Diagnostic Division, AtheroPoint
6. Department of Health Promotion, School of Medicine, Mother and Child Care and Medical Specialties (Promise), University of Palermo
7. Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia,, University of Belgrade
Issue: Vol 31, No 42 (2024)
Pages: 6926-6956
Section: Anti-Infectives and Infectious Diseases
URL: https://rjsvd.com/0929-8673/article/view/645150
DOI: https://doi.org/10.2174/0109298673262124231102042914
ID: 645150

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Abstract

:Cardiovascular disease (CDV) represents the major cause of death globally. Atherosclerosis, as the primary cause of CVD, is a chronic immune-inflammatory disorder with complex multifactorial pathophysiology encompassing oxidative stress, enhanced immune-inflammatory cascade, endothelial dysfunction, and thrombosis. An initiating event in atherosclerosis is the subendothelial accumulation of low-density lipoprotein (LDL), followed by the localization of macrophages to fatty deposits on blood vessel walls, forming lipid-laden macrophages (foam cells) that secrete compounds involved in plaque formation. Given the fact that foam cells are one of the key culprits that underlie the pathophysiology of atherosclerosis, special attention has been paid to the investigation of the efficient therapeutic approach to overcome the dysregulation of metabolism of cholesterol in macrophages, decrease the foam cell formation and/or to force its degradation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory serine proteinase that has emerged as a significant regulator of the lipid metabolism pathway. PCSK9 activation leads to the degradation of LDL receptors (LDLRs), increasing LDL cholesterol (LDL-C) levels in the circulation. PCSK9 pathway dysregulation has been identified as one of the mechanisms involved in atherosclerosis. In addition, microRNAs (miRNAs) are investigated as important epigenetic factors in the pathophysiology of atherosclerosis and dysregulation of lipid metabolism. This review article summarizes the recent findings connecting the role of PCSK9 in atherosclerosis and the involvement of various miRNAs in regulating the expression of PCSK9-related genes. We also discuss PCSK9 pathway-targeting therapeutic interventions based on PCSK9 inhibition, and miRNA levels manipulation by therapeutic agents.

Keywords

Atherosclerosis, cardiovascular disease, dyslipidemia, miRNA, PCSK9, therapeutic interventions, gene editing.

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The Link between miRNAs and PCKS9 in Atherosclerosis

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About the authors

Mirjana Macvanin

Zoran Gluvic

Aleksandra Klisic

Mia Manojlovic

Jasjit Suri

Manfredi Rizzo

Esma Isenovic

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