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.