Therapies Targeted at Non-Coding RNAs in Prevention and Limitation of Myocardial Infarction and Subsequent Cardiac Remodeling-Current Experience and Perspectives.

Michal Kowara,Agnieszka Cudnoch-Jedrzejewska,Sonia Borodzicz-Jazdzyk,Karolina Rybak,Maciej Kubik

doi:10.3390/ijms22115718

Therapies Targeted at Non-Coding RNAs in Prevention and Limitation of Myocardial Infarction and Subsequent Cardiac Remodeling-Current Experience and Perspectives.

Michal Kowara, Agnieszka Cudnoch-Jedrzejewska + Show 3 more

Open Access

https://doi.org/10.3390/ijms22115718

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Abstract

Myocardial infarction is one of the major causes of mortality worldwide and is a main cause of heart failure. This disease appears as a final point of atherosclerotic plaque progression, destabilization, and rupture. As a consequence of cardiomyocytes death during the infarction, the heart undergoes unfavorable cardiac remodeling, which results in its failure. Therefore, therapies aimed to limit the processes of atherosclerotic plaque progression, cardiac damage during the infarction, and subsequent remodeling are urgently warranted. A hopeful therapeutic option for the future medicine is targeting and regulating non-coding RNA (ncRNA), like microRNA, circular RNA (circRNA), or long non-coding RNA (lncRNA). In this review, the approaches targeted at ncRNAs participating in the aforementioned pathophysiological processes involved in myocardial infarction and their outcomes in preclinical studies have been concisely presented.

Highlights

The entire human genome is composed of approximately3.2 billion of base pairs, and only 30 million of bp are exonic sequences which encode mRNA particles translated to proteins [1,2]
This study showed that injection of sh-RAPIA carried by adenoviral AAV2/9 vectors to 24-week-old ApoE−/− mice resulted in reduction of lipid and macrophage accumulation, decrease of plaque size, and increase of collagen content
Therapies which targets ncRNA particles regulating the processes of myocardial cell death and adverse cardiac remodeling are under investigation in preclinical models

Summary

Introduction

3.2 billion of base pairs (bp), and only 30 million (ca. 1%) of bp are exonic sequences (i.e., genes) which encode mRNA particles translated to proteins [1,2]. It is known that these DNA fragments play an important role in regulation of the genes expression at different levels, i.e., chromatin organization and transcription factors binding, as well as direct influence upon mRNA transcripts and the process of their translation [3]. The ncRNAs are divided into long non-coding RNAs (lncRNAs) and short non-coding RNAs, with the microRNAs (miRNAs or miRs) as, currently, the best known group. These two groups differ from each other in the number of forming nucleotides with 200 nucleotides as a categorizing number [6]. The second group of inhibitors are small interfering RNAs (siRNAs)—short double-stranded RNA particles which induce target miRNA or lncRNA degradation mediated through RISC complex [16]. ASO: ◦ shRNA (short hairpin RNA) lncRNA ◦ ‘gapmer’ (central DNA ‘gap region’) siRNA (RNA interference)

The ncRNA as Potential Targets in Therapy of Atherosclerosis

Targeting ncRNA Regulating the Process of Myocardial Infarction

Preclinical Studies Examples

Challenges in Therapies Aimed to ncRNA

Findings

Conclusions