Non-coding RNA as Therapeutic Target: A Game Changer in Cardiac Regenerative Strategies?

The adult heart has a limited capacity to replace or regenerate damaged cardiac tissue following severe myocardial injury. Thus, therapies facilitating the induction of cardiac regeneration holds great promise for the treatment of end-stage heart failure, and for pathologies invoking severe cardiac dysfunction as a result of cardiomyocyte death. Recently, a number of studies have demonstrated that cardiac regeneration can be achieved through modulation and/or reprogramming of cardiomyocyte proliferation, differentiation, and survival signaling. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are reported to play critical roles in regulating key aspects of cardiomyocyte physiologic and pathologic signaling, including the regulation of cardiac regeneration both in vitro and in vivo. In this review, we will explore and detail the current understanding of ncRNA function in cardiac regeneration, and highlight established and novel strategies for the treatment of heart failure through modulation of ncRNAs-driven cardiac regeneration.

6,270 views

31 citations

Mini Review

10 March 2021

Novel Insights Linking lncRNAs and Metabolism With Implications for Cardiac Regeneration

Magda Correia

, 1 more and

Sandrina Nóbrega-Pereira

3,695 views

3 citations

Mini Review

20 January 2021

Francisco Santos

, 2 more and

Bruno Bernardes de Jesus

3,526 views

8 citations

Mini Review

29 September 2020

Circular RNAs in Cardiac Regeneration: Cardiac Cell Proliferation, Differentiation, Survival, and Reprogramming

Julia Mester-Tonczar

, 8 more and

Mariann Gyöngyösi

5,509 views

18 citations

Review

25 September 2020

Extracellular Vesicle miRNAs in the Promotion of Cardiac Neovascularisation

Despoina Kesidou

, 4 more and

Andrew Howard Baker

Cardiovascular disease (CVD) is the leading cause of mortality worldwide claiming almost 17. 9 million deaths annually. A primary cause is atherosclerosis within the coronary arteries, which restricts blood flow to the heart muscle resulting in myocardial infarction (MI) and cardiac cell death. Despite substantial progress in the management of coronary heart disease (CHD), there is still a significant number of patients developing chronic heart failure post-MI. Recent research has been focused on promoting neovascularisation post-MI with the ultimate goal being to reduce the extent of injury and improve function in the failing myocardium. Cardiac cell transplantation studies in pre-clinical models have shown improvement in cardiac function; nonetheless, poor retention of the cells has indicated a paracrine mechanism for the observed improvement. Cell communication in a paracrine manner is controlled by various mechanisms, including extracellular vesicles (EVs). EVs have emerged as novel regulators of intercellular communication, by transferring molecules able to influence molecular pathways in the recipient cell. Several studies have demonstrated the ability of EVs to stimulate angiogenesis by transferring microRNA (miRNA, miR) molecules to endothelial cells (ECs). In this review, we describe the process of neovascularisation and current developments in modulating neovascularisation in the heart using miRNAs and EV-bound miRNAs. Furthermore, we critically evaluate methods used in cell culture, EV isolation and administration.

8,952 views

36 citations

Original Research

21 August 2020

MicroRNA Expression Profiling of Bone Marrow–Derived Proangiogenic Cells (PACs) in a Mouse Model of Hindlimb Ischemia: Modulation by Classical Cardiovascular Risk Factors

Michel Desjarlais

, 3 more and

Alain Rivard

2,908 views

4 citations

Systematic Review

14 August 2020

Value of Blood-Based microRNAs in the Diagnosis of Acute Myocardial Infarction: A Systematic Review and Meta-Analysis

ChuanNan Zhai

, 9 more and

HongLiang Cong

Background: Recent studies have shown that blood-based miRNAs are dysregulated in patients with acute myocardial infarction (AMI) and are therefore a potential tool for the diagnosis of AMI. Therefore, this study summarized and evaluated studies focused on microRNAs as novel biomarkers for the diagnosis of AMI from the last ten years.

Methods: MEDLINE, the Cochrane Central database, and EMBASE were searched between January 2010 and December 2019. Studies that assessed the diagnostic accuracy of circulating microRNAs in AMI were chosen. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were used to assess the test performance of miRNAs.

Results: A total of 58 studies that included 8,206 participants assessed the diagnostic accuracy of circulating miRNAs in AMI. The main results of the meta-analyses are as follows: (1) Total miRNAs: the overall pooled sensitivity and specificity were 0.82 (95% CI: 0.79–0.85) and 0.87 (95% CI: 0.84–0.90), respectively. The AUC value was 0.91 (95% CI: 0.88–0.93) in the overall summary receiver operator characteristic (SROC) curve. (2) The panel of two miRNAs: sensitivity: 0.88 (95% CI: 0.77–0.94), specificity: 0.84 (95% CI: 0.72–0.91), AUC: 0.92 (95% CI: 0.90–0.94). (3) The panel of three miRNAs: sensitivity: 0.91 (95% CI: 0.85–0.94), specificity: 0.87 (95% CI: 0.77–0.92), AUC: 0.92 (95% CI: 0.89–0.94). (4) Results by types of miRNAs: miRNA-1: sensitivity: 0.78 (95% CI: 0.71–0.84), specificity: 0.86 (95% CI: 0.77–0.91), AUC: 0.88 (95% CI: 0.85–0.90); miRNA-133a: sensitivity: 0.85 (95% CI: 0.69–0.94), specificity: 0.92 (95% CI: 0.61–0.99), AUC: 0.93 (95% CI: 0.91–0.95); miRNA-208b: sensitivity: 0.80 (95% CI: 0.69–0.88), specificity: 0.96 (95% CI: 0.77–0.99), AUC: 0.91 (95% CI: 0.88–0.93); miRNA-499: sensitivity: 0.85 (95% CI: 0.77–0.91), specificity: 0.95 (95% CI: 0.89–0.98), AUC: 0.96 (95% CI: 0.94–0.97).

Conclusion: miRNAs may be used as potential biomarkers for the detection of AMI. For single, stand-alone miRNAs, miRNA-499 may have better diagnostic accuracy compared to other miRNAs. We propose that a panel of multiple miRNAs with high sensitivity and specificity should be tested.

5,478 views

20 citations

Original Research

16 June 2020

Loss of miR-132/212 Has No Long-Term Beneficial Effect on Cardiac Function After Permanent Coronary Occlusion in Mice

Zhiyong Lei

, 6 more and

Joost P. G. Sluijter

3,063 views

6 citations

Original Research

29 May 2020

Differential Expression and Bioinformatics Analysis of CircRNA in PDGF-BB-Induced Vascular Smooth Muscle Cells

Jiangtian Tian

, 8 more and

Jinwei Tian

Atherosclerosis is mediated by various factors and plays an important pathological foundation for cardiovascular and cerebrovascular diseases. Abnormal vascular smooth muscle cells (VSMCs) proliferation and migration have an essential role in atherosclerotic lesion formation. Circular RNAs (circRNA) have been widely detected in different species and are closely related to various diseases. However, the expression profiles and molecular regulatory mechanisms of circRNAs in VSMCs are still unknown. We used high-throughput RNA-seq as well as bioinformatics tools to systematically analyze circRNA expression profiles in samples from different VSMC phenotypes. Polymerase chain reaction (PCR), Sanger sequencing, and qRT-PCR were performed for circRNA validation. A total of 22191 circRNAs corresponding to 6273 genes (host genes) in the platelet-derived growth factor (PDGF-BB) treated group, the blank control group or both groups, were detected, and 112 differentially expressed circRNAs were identified between the PDGF-BB treated and control groups, of which 59 were upregulated, and 53 were downregulated. We selected 9 circRNAs for evaluation of specific head-to-tail splicing, and 10 differentially expressed circRNAs between the two groups for qRT-PCR validation. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses enrichment analyses revealed that the parental genes of the circRNAs mainly participated in cardiac myofibril assembly and positive regulation of DNA-templated transcription, indicating that they might be involved in cardiovascular diseases. Finally, we constructed a circRNA-miRNA network based on the dysregulated circRNAs and VSMC-related microRNAs. Our study is the first to show the differential expression of circRNAs in PDGF-BB-induced VSMCs and may provide new ideas and targets for the prevention and therapy of vascular diseases.

6,101 views

27 citations

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