Figure - available from: Frontiers in Cardiovascular Medicine
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Illustration of the process of microRNA (miRNA) biogenesis and function, described in miRNA biogenesis and functions (DGCR8, DiGeorge syndrome critical region gene 8; RISC, RNA-induced silencing complex; pri-miRNA, primary miRNA; pre-miRNA, precursor microRNA).
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Heart failure (HF) describes a group of manifestations caused by the failure of heart function as a pump that supports blood flow through the body. MicroRNAs (miRNAs), as one type of non-coding RNA molecule, have crucial roles in the etiology of HF. Accordingly, miRNAs related to HF may represent potential novel therapeutic targets. In this review,...
Citations
... At the same time, the selection of microRNAs as diagnostic markers for moyamoya disease is based on the following three points. First, many literature reports confirm that microRNAs play an important role in the progression of many diseases, including tumors, eclampsia, neurodegeneration, and heart failure, as well as the diagnosis and treatment of various diseases [15][16][17][18]. Second, the stability of microRNAs is significantly higher than that of mRNA. ...
... First-generation Ads faced challenges due to their immunogenic nature, but subsequent iterations proved more promising. Ad-based miRNA delivery has been notably successful in mitigating cardiomyocyte hypertrophy in mice [166,167]. In contrast, adeno-associated viruses (AAVs) are recognized for being nonpathogenic and exhibiting reduced immunogenicity. ...
Depression is a major contributor to the overall global burden of disease. The discovery of biomarkers for diagnosis or prediction of treatment responses and as therapeutic agents is a current priority. Previous studies have demonstrated the importance of short RNA molecules in the etiology of depression. The most extensively researched of these are microRNAs, a major component of cellular gene regulation and function. MicroRNAs function in a temporal and tissue-specific manner to regulate and modify the post-transcriptional expression of target mRNAs. They can also be shuttled as cargo of extracellular vesicles between the brain and the blood, thus informing about relevant mechanisms in the CNS through the periphery. In fact, studies have already shown that microRNAs identified peripherally are dysregulated in the pathological phenotypes seen in depression. Our article aims to review the existing evidence on microRNA dysregulation in depression and to summarize and evaluate the growing body of evidence for the use of microRNAs as a target for diagnostics and RNA-based therapies.
... The non-polar and hydrophobic characteristics of the myocardial cytomembrane represent an enormous challenge to miRNA delivery for heart disease since miRNAs have a negative charge and are hydrophilic [169,170]. As a result, crossing the myocardial cytomembrane is essential to transferring miRNAs to their targets and generating effective miRNA therapies. ...
... Molecules must demonstrate low cytotoxicity, high transfection efficiency, and specificity to deliver miRNA effectively. In general, miRNA delivery vehicles can be classified into viral and non-viral vectors [170]. ...
For the past two decades since their discovery, scientists have linked microRNAs (miRNAs) to posttranscriptional regulation of gene expression in critical cardiac physiological and pathological processes. Multiple non-coding RNA species regulate cardiac muscle phenotypes to stabilize cardiac homeostasis. Different cardiac pathological conditions, including arrhythmia, myocardial infarction, and hypertrophy, are modulated by non-coding RNAs in response to stress or other pathological conditions. Besides, miRNAs are implicated in several modulatory signaling pathways of cardiovascular disorders including mitogen-activated protein kinase, nuclear factor kappa beta, protein kinase B (AKT), NOD-like receptor family pyrin domain-containing 3 (NLRP3), Jun N-terminal kinases (JNKs), Toll-like receptors (TLRs) and apoptotic protease-activating factor 1 (Apaf-1)/caspases. This review highlights the potential role of miRNAs as therapeutic targets and updates our understanding of their roles in the processes underlying pathogenic phenotypes of cardiac muscle.
... Since the discovery of miRNAs in Caenorhabditis elegans in 1993 [38], miRNA research has intensified in recent years. This has led to the usage of miRNAs as diagnostic biomarkers and potential therapeutic targets for various diseases, including cardiovascular disease [39][40][41]. In the context of fibrosis, the specific term fibromiR is used to describe the group of miRNAs involved in fibrosis, including miR-1, miR-21, miR-29, and miR-208 [42]. ...
The cardiopulmonary system delivers oxygen throughout the body via blood circulation. It is an essential part of the body to sustain the lives of organisms. The integral parts of the cardiopulmonary system—the heart and lungs—are constantly exposed to damaging agents (e.g., dust, viruses), and can be greatly affected by injuries caused by dysfunction in tissues (e.g., myocardial infarction). When damaged, mesenchymal cells, such as fibroblasts, are activated to become myofibroblasts to initiate fibrosis as part of a regenerative mechanism. In diseased states, the excess accumulation of extracellular matrices secreted by myofibroblasts results in further dysfunction in the damaged organs. These fibrotic tissues cannot easily be removed. Thus, there is a growing interest in understanding the fibrotic process, as well as finding biomolecules that can be targets for slowing down or potentially stopping fibrosis. Among these biomolecules, the interest in studying long non-coding RNAs (lncRNAs; any non-protein-coding RNAs longer than 200 nucleotides) has intensified in recent years. In this commentary, we summarize the current status of lncRNA research in the cardiopulmonary system by focusing on cardiac and pulmonary fibrosis.
... MicroRNAs (miRNAs) are natural, endogenous small (20-22 nucleotides in length) noncoding endogenous RNAs that inhibit the expression of specific mRNA targets through Watson-Crick base pairing between the miRNA seed region and sequences commonly located in the 3′ untranslated regions (UTRs) [8,9]. MiRNAs have been increasingly recognized as an important class of regulatory small noncoding RNAs, in both physiological and pathological conditions in the heart, and have been implicated in the regulation of cardiomyocyte function because they are differentially expressed in several heart diseases, including HCM [10]. ...
... HCM is an inherited cardiovascular disease caused by a single gene mutation with predominantly an autosomal dominant pattern of inheritance, characterized by cardiac remodelling that is the basic mechanism of HCM and the process of changes in heart size, shape and function, and responds to internal and external cardiovascular injury or risk factors [9,19,20]. Pathological ventricular remodelling has three main characteristics: extensive fibrosis, pathological cardiomyocyte hypertrophy and cardiomyocyte apoptosis [21]. Recent studies have shown that miRNAs play a regulatory role in the above pathological ventricular remodelling [9,21] (Fig. 1). ...
... Pathological ventricular remodelling has three main characteristics: extensive fibrosis, pathological cardiomyocyte hypertrophy and cardiomyocyte apoptosis [21]. Recent studies have shown that miRNAs play a regulatory role in the above pathological ventricular remodelling [9,21] (Fig. 1). Xu et al. showed that miRNA-17-5p mainly regulates the expression and function of the mitochondrial fusion protein mitofusin 2 (MFN2) [22]. ...
Hypertrophic cardiomyopathy (HCM) is the most common heritable cardiomyopathy and is characterized by increased left ventricular wall thickness, but existing diagnostic and treatment approaches face limitations. MicroRNAs (miRNAs) are type of noncoding RNA molecule that plays crucial roles in the pathological process of cardiac remodelling. Accordingly, miRNAs related to HCM may represent potential novel therapeutic targets. In this review, we first discuss the different roles of miRNAs in the development of HCM. We then summarize the roles of common miRNAs as diagnostic and clinical biomarkers in HCM. Finally, we outline current and future challenges and potential new directions for miRNA-based therapeutics for HCM.
... are a class of endogenous, small, noncoding RNAs of 19-25 nucleotides (Zhou et al., 2021). Generally, miRs regulate gene functions at the posttranscriptional level by binding to the 5′ or 3′-untranslated regions of target mRNAs (Maegdefessel, 2014;Quiat & Olson, 2013;Scrutinio et al., 2017), and the miR-induced RNA-induced silencing complex (RISC) then suppresses the translation of the target mRNA or promotes its degradation (Krol et al., 2010). ...
Tanshinone IIA (TAN) is widely employed for handling cardiovascular disorders. The current study explored the potential role of miRs in the antifibrotic effect of TAN on heart. Fibrotic features were induced in cardiac fibroblasts (CFs) and in rat hearts, and then handled with TAN. MicroRNAs (miRs) responding to TAN were determined using a microarray assay. The selected miR was modulated to verify its role in antifibrotic effects of TAN. TAN suppressed the viability and the production of α-SMA in CFs, which was associated with 101 miR being upregulated and 223 miR being downregulated. MiR-618 was selected as the potential target of TAN. Ang II inhibited miR-618 level and resulted in the upregulation of pro-fibrosis factors, which was reversed by TAN. The antifibrotic effect of TAN was weakened by miR-618 inhibition. TAN inhibits hypertrophy and collagen deposition in heart tissues, which is associated with the increased level of miR-618.
Practical applications
The findings outlined in the current study show that the antifibrotic function of TAN is closely related to the function of miRs: the induction of miR-618 is indispensable for the function of TAN against the fibrotic process after heart injury, which will promote the application of TAN as an adjuvant therapy for improving heart function.
Noncoding RNAs (ncRNAs), which include circular RNAs (circRNAs) and microRNAs (miRNAs), regulate the development of cardiovascular diseases (CVD). Notably, circRNAs can interact with miRNAs, influencing their specific mRNA targets’ levels and shaping a competing endogenous RNAs (ceRNA) network. However, these interactions and their respective functions remain largely unexplored in ischemic heart failure (IHF). This study is aimed at identifying circRNA-centered ceRNA networks in non-end-stage IHF. Approximately 662 circRNA-miRNA-mRNA interactions were identified in the heart by combining state-of-the-art bioinformatics tools with experimental data. Importantly, KEGG terms of the enriched mRNA indicated CVD-related signaling pathways. A specific network centered on circBPTF was validated experimentally. The levels of let-7a-5p, miR-18a-3p, miR-146b-5p, and miR-196b-5p were enriched in circBPTF pull-down experiments, and circBPTF silencing inhibited the expression of HDAC9 and LRRC17, which are targets of miR-196b-5p. Furthermore, as suggested by the enriched pathway terms of the circBPTF ceRNA network, circBPTF inhibition elicited endothelial cell cycle arrest. circBPTF expression increased in endothelial cells exposed to hypoxia, and its upregulation was confirmed in cardiac samples of 36 end-stage IHF patients compared to healthy controls. In conclusion, circRNAs act as miRNA sponges, regulating the functions of multiple mRNA targets, thus providing a novel vision of HF pathogenesis and laying the theoretical foundation for further experimental studies.
Myocardial infarction is one of the major causes of morbidity and mortality worldwide. Current treatments can relieve the symptoms of myocardial ischemia but cannot repair the necrotic myocardial tissue. Novel therapeutic strategies based on cellular therapy, extracellular vesicles, non-coding RNAs and growth factors have been designed to restore cardiac function while inducing cardiomyocyte cycle re-entry, ensuring angiogenesis and cardioprotection, and preventing ventricular remodeling. However, they face low stability, cell engraftment issues or enzymatic degradation in vivo, and it is thus essential to combine them with biomaterial-based delivery systems. Microcarriers, nanocarriers, cardiac patches and injectable hydrogels have yielded promising results in preclinical studies, some of which are currently being tested in clinical trials. In this review, we cover the recent advances made in cellular and acellular therapies used for cardiac repair after MI. We present current trends in cardiac tissue engineering related to the use of microcarriers, nanocarriers, cardiac patches and injectable hydrogels as biomaterial-based delivery systems for biologics. Finally, we discuss some of the most crucial aspects that should be addressed in order to advance towards the clinical translation of cardiac tissue engineering approaches.
The renin angiotensin system (RAS) is well-known for its function in blood pressure regulation and its association with numerous cardiovascular diseases (CVDs). Dysregulation of the RAS can result in hypertension, subsequently promoting cardiovascular disorders, including hypertrophy, cardiac fibrosis, and heart failure. During the Coronavirus disease 2019 (COVID-19) pandemic, further functions of the RAS came to attention, as it was associated with the viral entry. Moreover, the RAS has always been of great research interest due to its importance in physiology. Advances in research have revealed that in addition to the canonical RAS, several organs, for instance, the heart, appear to have their own local RAS. Furthermore, technical advances have led to the discovery of new RAS components and a greater understanding of their interactions and epigenetic regulation. Several mechanisms are associated with epigenetics, including histone modification, DNA methylation, and non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). The role of epigenetic modifications and miRNAs has been of great research interest since miRNAs and their possible functions were discovered. In addition to established laboratory methods, new methods such as next-generation sequencing and bioinformatics provide the necessary tools for finding novel miRNAs with therapeutic value as biomarkers of disease or potential medication. Thus, we aim to give a brief overview of RAS-related miRNAs and their impact on CVDs.KeywordsRenin angiotensin systemmiRNAsEpigenetic regulationTherapeutic targetsHeart failureHypertrophyFibrosisHypertensionCardiovascular diseaseCOVID-19
