Евразийский Кардиологический Журнал (Oct 2023)
MicroRNA: a clinician’s view of the state of the problem. Part 3: MicroRNA and approaches to the treatment of cardiovascular diseases
Abstract
Cardiovascular diseases are one of the most common causes of death in both developing and developed countries of the world. Despite the improvement in primary prevention, the prevalence of cardiovascular diseases has continued to grow in recent years. Therefore, it is extremely important both to study the molecular pathophysiology of cardiovascular diseases in depth and to find new methods for early and appropriate prevention, diagnosis and treatment of these diseases. In the last decade, a large amount of research has focused on the study of microRNAs as potential diagnostic biomarkers, as well as their role in the treatment of cardiovascular diseases. microRNAs are endogenous small (21-23 nucleotides) ribonucleotides involved in the regulation of protein synthesis from amino acids based on matrix RNA. microRNAs are involved in the regulation of the expression of the majority (>60%) of genes encoding proteins, mainly due to its suppression, modulate numerous signaling pathways and cellular processes and participate in intercellular communication. Along with this, the important role of microRNAs in the cardiovascular system has been proven: participation in the regulation of processes such as angiogenesis, contractility of heart cells, control of lipid metabolism, the rate of fibrosis and atherosclerosis, which makes it possible to use microRNAs as therapeutic agents. Thus, the article considers the issue of the availability of several approaches to treatment involving microRNAs: overexpression of exogenous microRNAs to reduce the expression of genes with undesirable properties, overexpression of microRNA inhibitors, the use of «false» microRNAs or «sponges» that act as competitive inhibitors. The use of viruses with a positive (semantic) RNA chain resembling endogenous mRNAs is also considered.The author pays special attention to the important role of microRNAs in a number of cardiovascular diseases: microRNA-based therapy has been demonstrated in the treatment of diseases such as heart failure, dyslipidemia, acute coronary syndrome, arterial hypertension, as well as arterial hypertension caused by OSA. Studies proving the positive effect of microRNAs on slowing down the development of atherosclerosis are considered, which may allow them to be used as new therapeutic agents that can lead to optimization of approaches to the treatment of cardiovascular diseases. Particularly active is the development of drugs based on RNA interference (RNAi), which use recently discovered pathways of endogenous short interfering RNAs and become universal tools for effective suppression of protein expression. Thus, the use of certain drugs based on RNA interference in a number of clinical studies has shown a significant decrease in the level of non-HDL cholesterol and triglycerides in the treatment of dyslipidemia and NT-proBNP in the treatment of hereditary transtyretin amyloidosis. This article touches upon the issue of such an important problem as myocardial infarction. Thus, hypertrophy and fibrosis of the heart significantly contribute to thickening and increasing the rigidity of the ventricular walls, leading to remodeling of the heart and worsening the prognosis. For this purpose, a biocompatible patch with microneedles (MI) with antifibrotic activity based on microRNA can be used to prevent excessive cardiac fibrosis after myocardial infarction. Summarizing the above, it is certainly worth noting that this problem has been little studied and requires further research. Identifying a safe and effective strategy for microRNA-based therapy remains a difficult task, but the new approaches considered have enormous potential for the treatment of cardiovascular diseases.
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