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MicroRNA in Cardiac Health and Disease
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MicroRNA in Cardiac Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 21879

Special Issue Editors

Dr. Letizia Pitto

E-Mail
Guest Editor
Institute of Clinical Physiology CNR, Pisa, Italy
Interests: post-transcriptional regulation of gene expression; noncoding RNA; congenital heart disease; animal models
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Forini

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Guest Editor
CNR Institute of Clinical Physiology, Via G.Moruzzi 1, 56100 Pisa, Italy
Interests: molecular mechanisms in cardiovascular disease, diabetic retinopathy; idiopathic pulmonary hypertension, thyroid/heart axis; mitochondria physiology and pathophysiology; non coding RNA, animal models
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

High-throughput RNA sequencing technology revealed the key role played by noncoding RNAs as developmental and evolutionary determinants of organismal complexity. MiRNAs are crucial and the most thoroughly characterized component of noncoding RNAs. MiRNAs are ~20–22 nucleotides RNA molecules with post-transcriptionally regulatory roles in almost all physiological and pathological processes. Their evolutionary conservation confirms their importance as regulators, but also eased to get insight into miRNA action mechanisms by exploiting animal models.

Development of heart and cardiac function is a highly spatiotemporal regulated process which actively involves miRNA control. During the last 10 years, alterations in the expression of tens of miRNAs have been described for different cardiovascular diseases (CVDs) such as hypertrophy, arrhythmias, and infarction but also in inherited cardiomyopathies. Modulations in response to stress or disease together with presence in body fluids make miRNAs particularly valuable cardiac biomarkers. More recently, several preclinical studies in animal models demonstrated the possibility to obtain cardioprotective effects by miRNA modulation. Indeed, cardiac microRNAs can affect cardiomyocyte regenerative capacity, inflammatory response or mitochondrial function after myocardial infarction; control pro-survival targets in heart of anthracycline-treated oncologic patients; affect systemic energy homeostasis in metabolic disorders; downregulate hypertrophic response and regulate contractile proteins or Ca homeostasis in cardiomyopathies. These results highlight the therapeutic potential of miRNAs, although many technical obstacles still need to be overcome before they can be approved for CVD treatment in humans.

This Special Issue, entitled “MicroRNA in Cardiac Health and Disease,” of IJMS will cover a selection of recent research topics related to the role of miRNAs in health and disease with a special focus on state-of-the-art miRNA-based therapeutic strategies in CVD. Up-to-date review articles, commentaries, and experimental papers are all welcome.

Dr. Letizia Pitto
Dr. Francesca Forini
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • MicroRNA
  • cardiac biomarker
  • cardiac therapeutic target
  • heart failure
  • arrhythmias
  • adverse remodeling
  • cardiomyopathy
  • cardiovascular risk factors

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Published Papers (7 papers)

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Editorial

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3 pages, 181 KiB  
Editorial
Editorial for Special Issue: “MicroRNA in Cardiac Health and Disease”
by Francesca Forini and Letizia Pitto
Int. J. Mol. Sci. 2022, 23(24), 15567; https://doi.org/10.3390/ijms232415567 - 8 Dec 2022
Cited by 1 | Viewed by 971
Abstract
MicroRNAs (miRNAs) are endogenous, evolutionarily conserved, non-coding RNA molecules that influence most, if not all biological events, with cardiovascular development and homeostasis being no exceptions [...] Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)

Research

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17 pages, 2254 KiB  
Article
miR-1183 Is a Key Marker of Remodeling upon Stretch and Tachycardia in Human Myocardium
by Natasa Djalinac, Ewald Kolesnik, Heinrich Maechler, Susanne Scheruebel-Posch, Brigitte Pelzmann, Peter P. Rainer, Ines Foessl, Markus Wallner, Daniel Scherr, Akos Heinemann, Simon Sedej, Senka Ljubojevic-Holzer, Dirk von Lewinski and Egbert Bisping
Int. J. Mol. Sci. 2022, 23(13), 6962; https://doi.org/10.3390/ijms23136962 - 23 Jun 2022
Cited by 4 | Viewed by 2214
Abstract
Many cardiac insults causing atrial remodeling are linked to either stretch or tachycardia, but a comparative characterization of their effects on early remodeling events in human myocardium is lacking. Here, we applied isometric stretch or sustained tachycardia at 2.5 Hz in human atrial [...] Read more.
Many cardiac insults causing atrial remodeling are linked to either stretch or tachycardia, but a comparative characterization of their effects on early remodeling events in human myocardium is lacking. Here, we applied isometric stretch or sustained tachycardia at 2.5 Hz in human atrial trabeculae for 6 h followed by microarray gene expression profiling. Among largely independent expression patterns, we found a small common fraction with the microRNA miR-1183 as the highest up-regulated transcript (up to 4-fold). Both, acute stretch and tachycardia induced down-regulation of the predicted miR-1183 target genes ADAM20 and PLA2G7. Furthermore, miR-1183 was also significantly up-regulated in chronically remodeled atrial samples from patients with persistent atrial fibrillation (3-fold up-regulation versus sinus rhythm samples), and in ventricular myocardium from dilative cardiomyopathy hearts (2-fold up-regulation) as compared to non-failing controls. In sum, although stretch and tachycardia show distinct transcriptomic signatures in human atrial myocardium, both cardiac insults consistently regulate the expression of miR-1183 and its downstream targets in acute and chronic remodeling. Thus, elevated expression of miR-1183 might serve as a tissue biomarker for atrial remodeling and might be of potential functional significance in cardiac disease. Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)
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15 pages, 2478 KiB  
Article
Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression
by Paola Canale, Giuseppina Nicolini, Letizia Pitto, Claudia Kusmic, Milena Rizzo, Silvana Balzan, Giorgio Iervasi and Francesca Forini
Int. J. Mol. Sci. 2022, 23(12), 6549; https://doi.org/10.3390/ijms23126549 - 11 Jun 2022
Cited by 7 | Viewed by 2201
Abstract
The opening of the ATP-sensitive mitochondrial potassium channel (mitok-ATP) is a common goal of cardioprotective strategies in the setting of acute and chronic myocardial disease. The biologically active thyroid hormone (TH), 3-5-3-triiodothyronine (T3), has been indicated as a potential activator of mitoK-ATP but [...] Read more.
The opening of the ATP-sensitive mitochondrial potassium channel (mitok-ATP) is a common goal of cardioprotective strategies in the setting of acute and chronic myocardial disease. The biologically active thyroid hormone (TH), 3-5-3-triiodothyronine (T3), has been indicated as a potential activator of mitoK-ATP but the underlying mechanisms are still elusive. Here we describe a novel role of T3 in the transcriptional regulation of mitoK and mitoSur, the recently identified molecular constituents of the channel. To mimic human ischemic heart damage, we used a rat model of a low T3 state as the outcome of a myocardial ischemia/reperfusion event, and neonatal rat cardiomyocytes (NRCM) challenged with hypoxia or H2O2. Either in the in vivo or in vitro models, T3 administration to recover the physiological concentrations was able to restore the expression level of both the channel subunits, which were found to be downregulated under the stress conditions. Furthermore, the T3-mediated transcriptional activation of mitoK-ATP in the myocardium and NRCM was associated with the repression of the TH-inactivating enzyme, deiodinase 3 (Dio3), and an up-regulation of the T3-responsive miR-133a-3p. Mechanistically, the loss and gain of function experiments and reporter gene assays performed in NRCM, have revealed a new regulatory axis whereby the silencing of Dio3 under the control of miR-133a-3p drives the T3-dependent modulation of cardiac mitoK and mitoSur transcription. Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)
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Review

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13 pages, 1007 KiB  
Review
miRNA in Ischemic Heart Disease and Its Potential as Biomarkers: A Comprehensive Review
by Amanda Shen-Yee Kong, Kok-Song Lai, Swee-Hua Erin Lim, Sivakumar Sivalingam, Jiun-Yan Loh and Sathiya Maran
Int. J. Mol. Sci. 2022, 23(16), 9001; https://doi.org/10.3390/ijms23169001 - 12 Aug 2022
Cited by 16 | Viewed by 2847
Abstract
Ischemic heart disease (IHD) constitutes the leading global cause of mortality and morbidity. Although significant progress has been achieved in the diagnosis, treatment, and prognosis of IHD, more robust diagnostic biomarkers and therapeutic interventions are still needed to circumvent the increasing incidence of [...] Read more.
Ischemic heart disease (IHD) constitutes the leading global cause of mortality and morbidity. Although significant progress has been achieved in the diagnosis, treatment, and prognosis of IHD, more robust diagnostic biomarkers and therapeutic interventions are still needed to circumvent the increasing incidence of IHD. MicroRNAs (miRNAs) are critical regulators of cardiovascular function and are involved in various facets of cardiovascular biology. While the knowledge of the role of miRNAs in IHD as diagnostic biomarkers has improved, research emphasis on how miRNAs can be effectively used for diagnosis and prognosis of IHD is crucial. This review provides an overview of the biology, therapeutic and diagnostic potential, as well as the caveats of using miRNAs in IHD based on existing research. Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)
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17 pages, 917 KiB  
Review
Role of miRNA-1 and miRNA-21 in Acute Myocardial Ischemia-Reperfusion Injury and Their Potential as Therapeutic Strategy
by Eranthi Jayawardena, Lejla Medzikovic, Gregoire Ruffenach and Mansoureh Eghbali
Int. J. Mol. Sci. 2022, 23(3), 1512; https://doi.org/10.3390/ijms23031512 - 28 Jan 2022
Cited by 29 | Viewed by 4329
Abstract
Coronary artery disease remains the leading cause of death. Acute myocardial infarction (MI) is characterized by decreased blood flow to the coronary arteries, resulting in cardiomyocytes death. The most effective strategy for treating an MI is early and rapid myocardial reperfusion, but restoring [...] Read more.
Coronary artery disease remains the leading cause of death. Acute myocardial infarction (MI) is characterized by decreased blood flow to the coronary arteries, resulting in cardiomyocytes death. The most effective strategy for treating an MI is early and rapid myocardial reperfusion, but restoring blood flow to the ischemic myocardium can induce further damage, known as ischemia-reperfusion (IR) injury. Novel therapeutic strategies are critical to limit myocardial IR injury and improve patient outcomes following reperfusion intervention. miRNAs are small non-coding RNA molecules that have been implicated in attenuating IR injury pathology in pre-clinical rodent models. In this review, we discuss the role of miR-1 and miR-21 in regulating myocardial apoptosis in ischemia-reperfusion injury in the whole heart as well as in different cardiac cell types with special emphasis on cardiomyocytes, fibroblasts, and immune cells. We also examine therapeutic potential of miR-1 and miR-21 in preclinical studies. More research is necessary to understand the cell-specific molecular principles of miRNAs in cardioprotection and application to acute myocardial IR injury. Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)
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14 pages, 314 KiB  
Review
Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective
by Perwez Alam, Bryan D. Maliken, Shannon M. Jones, Malina J. Ivey, Zhichao Wu, Yigang Wang and Onur Kanisicak
Int. J. Mol. Sci. 2021, 22(23), 13104; https://doi.org/10.3390/ijms222313104 - 3 Dec 2021
Cited by 19 | Viewed by 4056
Abstract
The limited ability of mammalian adult cardiomyocytes to proliferate following an injury to the heart, such as myocardial infarction, is a major factor that results in adverse fibrotic and myocardial remodeling that ultimately leads to heart failure. The continued high degree of heart [...] Read more.
The limited ability of mammalian adult cardiomyocytes to proliferate following an injury to the heart, such as myocardial infarction, is a major factor that results in adverse fibrotic and myocardial remodeling that ultimately leads to heart failure. The continued high degree of heart failure-associated morbidity and lethality requires the special attention of researchers worldwide to develop efficient therapeutics for cardiac repair. Recently, various strategies and approaches have been developed and tested to extrinsically induce regeneration and restoration of the myocardium after cardiac injury have yielded encouraging results. Nevertheless, these interventions still lack adequate success to be used for clinical interventions. This review highlights and discusses both cell-based and cell-free therapeutic approaches as well as current advancements, major limitations, and future perspectives towards developing an efficient therapeutic method for cardiac repair. Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)
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Graphical abstract

15 pages, 1588 KiB  
Review
MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review
by Alice Chiara Manetti, Aniello Maiese, Marco Di Paolo, Alessandra De Matteis, Raffaele La Russa, Emanuela Turillazzi, Paola Frati and Vittorio Fineschi
Int. J. Mol. Sci. 2021, 22(1), 321; https://doi.org/10.3390/ijms22010321 - 30 Dec 2020
Cited by 44 | Viewed by 4004
Abstract
Sepsis is a severe condition characterized by systemic inflammation. One of the most involved organs in sepsis is the heart. On the other hand, heart failure and dysfunction are some of the most leading causes of death in septic patients. miRNAs are short [...] Read more.
Sepsis is a severe condition characterized by systemic inflammation. One of the most involved organs in sepsis is the heart. On the other hand, heart failure and dysfunction are some of the most leading causes of death in septic patients. miRNAs are short single-strand non-coding ribonucleic acids involved in the regulation of gene expression on a post-transcriptional phase, which means they are a part of the epigenetic process. Recently, researchers have found that miRNA expression in tissues and blood differs depending on different conditions. Because of this property, their use as serum sepsis biomarkers has also been explored. A narrative review is carried out to gather and summarize what is known about miRNAs’ influence on cardiac dysfunction during sepsis. When reviewing the literature, we found at least 77 miRNAs involved in cardiac inflammation and dysfunction during sepsis. In the future, miRNAs may be used as early sepsis-induced cardiac dysfunction biomarkers or as new drug targets. This could help clinicians to early detect, prevent, and treat cardiac damage. The potential role of miRNAs as new diagnostic tools and therapeutic strategies worth deepening the complex network between non-coding RNA and biological pathways. Additional studies are needed to further investigate their role in sepsis-induced myocardium injury. Full article
(This article belongs to the Special Issue MicroRNA in Cardiac Health and Disease)
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