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RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 December 2020) | Viewed by 41994

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Special Issue Editors

Dr. Yvan Devaux

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Guest Editor

Cardiovascular Research Unit, Luxembourg Institute of Health, L-1445 Strassen, Luxembourg
Interests: microRNAs; cardiovascular disease
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Wolfram Doehner

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Co-Guest Editor

Charite - Universitatsmedizin Berlin, Center for Stroke Research Berlin, Berlin, Germany
Interests: metabolic pathophysiology; loss of muscle mass; cachexia and sarcopenia in chronic diseases

Dr. Fabio Martelli

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Co-Guest Editor

IRCCS Policlinico San Donato, Molecular Cardiology Laboratory, San Donato Milanese MI, Italy
Interests: microRNA; ischaemia; dystrophy; mRNA
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Inga Zerr

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Co-Guest Editor

Department of Neurology, University Medical Center, Georg August University, Göttingen, Germany
Interests: biomarkers; dementia; neurodegeneration; prion

Special Issue Information

Dear Colleagues,

The EU-CardioRNA COST Action CA17129 is an interdisciplinary network from 36 countries aiming to accelerate the understanding of transcriptomics in cardiovascular disease and further the translation of experimental data into usable applications to improve personalized medicine in this field. You can see more details at https://www.cost.eu/actions/CA17129/#tabs|Name:overview

Due to known interactions between the brain and the heart, members of the EU-CardioRNA COST Action aim to provide a forum for discussion around the topics of brain and heart diseases in this Special Issue of International Journal of Molecular Science.

Cerebro-cardio-vascular disease remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought.

We are looking for papers on the role or biomarker potential of RNAs, whether protein-coding or noncoding RNAs, in diseases affecting the brain, the heart, and/or the vascular system. Papers reporting or discussing common mechanisms or interactions between these vital organs are particularly welcome. This is, however, not a prerequisite to submit papers to this Special Issue. We invite contributions of reviews and/or original papers reporting recent efforts in the field of RNAs in Brain and Heart Diseases.

Prof. Dr. Yvan Devaux
Prof. Dr. Inga Zerr
Dr. Fabio Martelli
Prof. Wolfram Doehner, MD, PhD
Guest Editor

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

RNA
Noncoding RNA
Transcription
Transcriptomics
Epigenetics
RNA modifications
Brain disease
Vascular disease
Heart disease
Heart Failure
Diabetes
Stroke
Myocardial infarction
Parkinson disease
Alzheimer disease
Aging
Vascular Cognitive Impairment

Published Papers (13 papers)

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Editorial

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6 pages, 1397 KiB

Open AccessEditorial

RNAs in Brain and Heart Diseases

by Dimitris Beis, Inga Zerr, Fabio Martelli, Wolfram Doehner and Yvan Devaux

Int. J. Mol. Sci. 2020, 21(10), 3717; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103717 - 25 May 2020

Cited by 5 | Viewed by 3130

Abstract

In the era of single-cell analysis, one always has to keep in mind the systemic nature of various diseases and how these diseases could be optimally studied. Comorbidities of the heart in neurological diseases as well as of the brain in cardiovascular diseases are prevalent, but how interactions in the brain–heart axis affect disease development and progression has been poorly addressed. Several brain and heart diseases share common risk factors. A better understanding of the brain–heart interactions will provide better insights for future treatment and personalization of healthcare, for heart failure patients’ benefit notably. We review here emerging evidence that studying noncoding RNAs in the brain–heart axis could be pivotal in understanding these interactions. We also introduce the Special Issue of the International Journal of Molecular Sciences RNAs in Brain and Heart Diseases—EU-CardioRNA COST Action. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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Research

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22 pages, 5630 KiB

Open AccessArticle

A Comprehensive miRNome Analysis of Macrophages Isolated from db/db Mice and Selected miRNAs Involved in Metabolic Syndrome-Associated Cardiac Remodeling

by Justyna Niderla-Bielińska, Aneta Ścieżyńska, Aneta Moskalik, Ewa Jankowska-Steifer, Krzysztof Bartkowiak, Mateusz Bartkowiak, Ewelina Kiernozek, Anna Podgórska, Bogdan Ciszek, Barbara Majchrzak and Anna Ratajska

Int. J. Mol. Sci. 2021, 22(4), 2197; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042197 - 23 Feb 2021

Cited by 4 | Viewed by 3124

Abstract

Cardiac macrophages are known from various activities, therefore we presume that microRNAs (miRNAs) produced or released by macrophages in cardiac tissue have impact on myocardial remodeling in individuals with metabolic syndrome (MetS). We aim to assess the cardiac macrophage miRNA profile by selecting those miRNA molecules that potentially exhibit regulatory functions in MetS-related cardiac remodeling. Cardiac tissue macrophages from control and db/db mice (an animal model of MetS) were counted and sorted with flow cytometry, which yielded two populations: CD45⁺CD11b⁺CD64⁺Ly6C^hi and CD45⁺CD11b⁺CD64⁺Ly6C^low. Total RNA was then isolated, and miRNA expression profiles were evaluated with Next Generation Sequencing. We successfully sequenced 1400 miRNAs in both macrophage populations: CD45⁺CD11b⁺CD64⁺Ly6C^hi and CD45⁺CD11b⁺CD64⁺Ly6C^low. Among the 1400 miRNAs, about 150 showed different expression levels in control and db/db mice and between these two subpopulations. At least 15 miRNAs are possibly associated with MetS pathology in cardiac tissue due to direct or indirect regulation of the expression of miRNAs for proteins involved in angiogenesis, fibrosis, or inflammation. In this paper, for the first time we describe the miRNA transcription profile in two distinct macrophage populations in MetS-affected cardiac tissue. Although the results are preliminary, the presented data provide a foundation for further studies on intercellular cross-talk/molecular mechanism(s) involved in the regulation of MetS-related cardiac remodeling. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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16 pages, 4079 KiB

Open AccessArticle

Novel Transcript Discovery Expands the Repertoire of Pathologically-Associated, Long Non-Coding RNAs in Vascular Smooth Muscle Cells

by Matthew Bennett, Igor Ulitsky, Iraide Alloza, Koen Vandenbroeck, Vladislav Miscianinov, Amira Dia Mahmoud, Margaret Ballantyne, Julie Rodor and Andrew H. Baker

Int. J. Mol. Sci. 2021, 22(3), 1484; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031484 - 02 Feb 2021

Cited by 4 | Viewed by 3268

Abstract

Vascular smooth muscle cells (VSMCs) provide vital contractile force within blood vessel walls, yet can also propagate cardiovascular pathologies through proliferative and pro-inflammatory activities. Such phenotypes are driven, in part, by the diverse effects of long non-coding RNAs (lncRNAs) on gene expression. However, lncRNA characterisation in VSMCs in pathological states is hampered by incomplete lncRNA representation in reference annotation. We aimed to improve lncRNA representation in such contexts by assembling non-reference transcripts in RNA sequencing datasets describing VSMCs stimulated in vitro with cytokines, growth factors, or mechanical stress, as well as those isolated from atherosclerotic plaques. All transcripts were then subjected to a rigorous lncRNA prediction pipeline. We substantially improved coverage of lncRNAs responding to pro-mitogenic stimuli, with non-reference lncRNAs contributing 21–32% for each dataset. We also demonstrate non-reference lncRNAs were biased towards enriched expression within VSMCs, and transcription from enhancer sites, suggesting particular relevance to VSMC processes, and the regulation of neighbouring protein-coding genes. Both VSMC-enriched and enhancer-transcribed lncRNAs were large components of lncRNAs responding to pathological stimuli, yet without novel transcript discovery 33–46% of these lncRNAs would remain hidden. Our comprehensive VSMC lncRNA repertoire allows proper prioritisation of candidates for characterisation and exemplifies a strategy to broaden our knowledge of lncRNA across a range of disease states. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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14 pages, 2606 KiB

Open AccessCommunication

The Influence of the LINC00961/SPAAR Locus Loss on Murine Development, Myocardial Dynamics, and Cardiac Response to Myocardial Infarction

by Ana-Mishel Spiroski, Rachel Sanders, Marco Meloni, Ian R. McCracken, Adrian Thomson, Mairi Brittan, Gillian A. Gray and Andrew H. Baker

Int. J. Mol. Sci. 2021, 22(2), 969; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22020969 - 19 Jan 2021

Cited by 9 | Viewed by 2864

Abstract

Long non-coding RNAs (lncRNAs) have structural and functional roles in development and disease. We have previously shown that the LINC00961/SPAAR (small regulatory polypeptide of amino acid response) locus regulates endothelial cell function, and that both the lncRNA and micropeptide counter-regulate angiogenesis. To assess human cardiac cell SPAAR expression, we mined a publicly available scRNSeq dataset and confirmed LINC00961 locus expression and hypoxic response in a murine endothelial cell line. We investigated post-natal growth and development, basal cardiac function, the cardiac functional response, and tissue-specific response to myocardial infarction. To investigate the influence of the LINC00961/SPAAR locus on longitudinal growth, cardiac function, and response to myocardial infarction, we used a novel CRISPR/Cas9 locus knockout mouse line. Data mining suggested that SPAAR is predominantly expressed in human cardiac endothelial cells and fibroblasts, while murine LINC00961 expression is hypoxia-responsive in mouse endothelial cells. LINC00961^–/– mice displayed a sex-specific delay in longitudinal growth and development, smaller left ventricular systolic and diastolic areas and volumes, and greater risk area following myocardial infarction compared with wildtype littermates. These data suggest the LINC00961/SPAAR locus contributes to cardiac endothelial cell and fibroblast function and hypoxic response, growth and development, and basal cardiovascular function in adulthood. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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10 pages, 2451 KiB

Open AccessCommunication

Circulating tRNA Fragments as a Novel Biomarker Class to Distinguish Acute Stroke Subtypes

by T. Truc My Nguyen, M. Leontien van der Bent, Marieke J. H. Wermer, Ido R. van den Wijngaard, Erik W. van Zwet, Bas de Groot, Paul H. A. Quax, Nyika D. Kruyt and Anne Yaël Nossent

Int. J. Mol. Sci. 2021, 22(1), 135; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010135 - 24 Dec 2020

Cited by 14 | Viewed by 3257

Abstract

Early blood biomarkers to diagnose acute stroke could drastically reduce treatment delays. We investigated whether circulating small non-coding RNAs can serve as biomarkers to distinguish between acute ischemic stroke (IS), intracerebral hemorrhage (ICH) and stroke mimics (SM). In an ongoing observational cohort study, we performed small RNA-sequencing in plasma obtained from a discovery cohort of 26 patients (9 IS, 8 ICH and 9 SM) presented to the emergency department within 6 h of symptom onset. We validated our results in an independent dataset of 20 IS patients and 20 healthy controls. ICH plasma had the highest abundance of ribosomal and tRNA-derived fragments, while microRNAs were most abundant in plasma of IS patients. Combinations of four to five tRNAs yielded diagnostic accuracies (areas under the receiver operating characteristics curve) up to 0.986 (ICH vs. IS and SM) in the discovery cohort. Validation of the IS and SM models in the independent dataset yielded diagnostic accuracies of 0.870 and 0.885 to distinguish IS from healthy controls. Thus, we identified tRNA-derived fragments as a promising novel class of biomarkers to distinguish between acute IS, ICH and SM, as well as healthy controls. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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19 pages, 4610 KiB

Open AccessArticle

Increased miR-142 Levels in Plasma and Atherosclerotic Plaques from Peripheral Artery Disease Patients with Post-Surgery Cardiovascular Events

by Teodora Barbalata, Oriana E. Moraru, Camelia S. Stancu, Yvan Devaux, Maya Simionescu, Anca V. Sima and Loredan S. Niculescu

Int. J. Mol. Sci. 2020, 21(24), 9600; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249600 - 16 Dec 2020

Cited by 12 | Viewed by 1736

Abstract

There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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12 pages, 976 KiB

Open AccessArticle

Association of miR-21-5p, miR-122-5p, and miR-320a-3p with 90-Day Mortality in Cardiogenic Shock

by Mikko Hänninen, Toni Jäntti, Heli Tolppanen, Heli Segersvärd, Tuukka Tarvasmäki, Johan Lassus, Mélanie Vausort, Yvan Devaux, Alessandro Sionis, Ilkka Tikkanen, Veli-Pekka Harjola, Päivi Lakkisto and for the CardShock Study Group

Int. J. Mol. Sci. 2020, 21(21), 7925; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217925 - 26 Oct 2020

Cited by 10 | Viewed by 2371

Abstract

Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5–10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p < 0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1–3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2–3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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22 pages, 2928 KiB

Open AccessArticle

Transcriptomic Analysis of Age-Associated Periventricular Lesions Reveals Dysregulation of the Immune Response

by Motaz M. Fadul, Paul R. Heath, Johnathan Cooper-Knock, Julian M. Kurz, Hayder A. Al-Azzawi, Zarki Ali, Taylor Smith, Fiona E. Matthews, Carol Brayne, Stephen B. Wharton and Julie E. Simpson

Int. J. Mol. Sci. 2020, 21(21), 7924; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21217924 - 25 Oct 2020

Cited by 6 | Viewed by 2564

Abstract

White matter lesions (WML) are a common feature of the ageing brain associated with cognitive impairment. The gene expression profiles of periventricular lesions (PVL, n = 7) and radiologically-normal-appearing (control) periventricular white matter cases (n = 11) obtained from the Cognitive Function and Ageing Study (CFAS) neuropathology cohort were interrogated using microarray analysis and NanoString to identify novel mechanisms potentially underlying their formation. Histological characterisation of control white matter cases identified a subgroup (n = 4) which contained high levels of MHC-II immunoreactive microglia, and were classified as “pre-lesional.” Microarray analysis identified 2256 significantly differentially-expressed genes (p ≤ 0.05, FC ≥ 1.2) in PVL compared to non-lesional control white matter (1378 upregulated and 878 downregulated); 2649 significantly differentially-expressed genes in “pre-lesional” cases compared to PVL (1390 upregulated and 1259 downregulated); and 2398 significantly differentially-expressed genes in “pre-lesional” versus non-lesional control cases (1527 upregulated and 871 downregulated). Whilst histological evaluation of a single marker (MHC-II) implicates immune-activated microglia in lesion pathology, transcriptomic analysis indicates significant downregulation of a number of activated microglial markers and suggests established PVL are part of a continuous spectrum of white matter injury. The gene expression profile of “pre-lesional” periventricular white matter suggests upregulation of several signalling pathways may be a neuroprotective response to prevent the pathogenesis of PVL. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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16 pages, 1019 KiB

Open AccessArticle

Uncharacterized RNAs in Plasma of Alzheimer’s Patients Are Associated with Cognitive Impairment and Show a Potential Diagnostic Power

by Cristina Barbagallo, Maria Teresa Di Martino, Margherita Grasso, Maria Grazia Salluzzo, Francesca Scionti, Filomena Irene Ilaria Cosentino, Giuseppe Caruso, Davide Barbagallo, Cinzia Di Pietro, Raffaele Ferri, Filippo Caraci, Michele Purrello and Marco Ragusa

Int. J. Mol. Sci. 2020, 21(20), 7644; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21207644 - 15 Oct 2020

Cited by 8 | Viewed by 2401

Abstract

Alzheimer’s disease (AD) diagnosis is actually based on clinical evaluation and brain-imaging tests, and it can often be confirmed only post-mortem. Therefore, new non-invasive molecular biomarkers are necessary to improve AD diagnosis. As circulating microRNA biomarkers have been proposed for many diseases, including AD, we aimed to identify new diagnostic non-small RNAs in AD. Whole transcriptome analysis was performed on plasma samples of five AD and five unaffected individuals (CTRL) using the Clariom D Pico Assay, followed by validation in real-time PCR on 37 AD patients and 37 CTRL. Six differentially expressed (DE) transcripts were identified: GS1-304P7.3 (upregulated), NONHSAT090268, TC0100011037, TC0400008478, TC1400008125, and UBE2V1 (downregulated). Peripheral blood mononuclear cells (PBMCs) may influence the expression of circulating RNAs and their analysis has been proposed to improve AD clinical management. Accordingly, DE transcript expression was also evaluated in PBMCs, showing no difference between AD and CTRL. ROC (receiver operating characteristic) curve analysis was performed to evaluate the diagnostic accuracy of each DE transcript and a signature including all of them. A correlation between cognitive impairment and GS1-304P7.3, NONHSAT090268, TC0100011037, and TC0400008478 was detected, suggesting a potential association between their extracellular abundance and AD clinical phenotype. Finally, this study identified six transcripts showing altered expression in the plasma of AD patients. Given the need for new, accurate blood biomarkers for AD diagnosis, these transcripts may be considered for further analyses in larger cohorts, also in combination with other biomarkers, aiming to identify specific RNA-based biomarkers to be eventually applied to clinical practice. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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9 pages, 1138 KiB

Open AccessArticle

Circulating Levels of Brain-Enriched MicroRNAs Correlate with Neuron Specific Enolase after Cardiac Arrest—A Substudy of the Target Temperature Management Trial

by Francesca Maria Stefanizzi, Niklas Nielsen, Lu Zhang, Josef Dankiewicz, Pascal Stammet, Patrik Gilje, David Erlinge, Christian Hassager, Matthew P. Wise, Michael Kuiper, Hans Friberg, Yvan Devaux and Antonio Salgado-Somoza

Int. J. Mol. Sci. 2020, 21(12), 4353; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124353 - 19 Jun 2020

Cited by 5 | Viewed by 2723

Abstract

Outcome prognostication after cardiac arrest (CA) is challenging. Current multimodal prediction approaches would benefit from new biomarkers. MicroRNAs constitute a novel class of disease markers and circulating levels of brain-enriched ones have been associated with outcome after CA. To determine whether these levels reflect the extent of brain damage in CA patients, we assessed their correlation with neuron-specific enolase (NSE), a marker of brain damage. Blood samples taken 48 h after return of spontaneous circulation from two groups of patients from the Targeted Temperature Management trial were used. Patients were grouped depending on their neurological outcome at six months. Circulating levels of microRNAs were assessed by sequencing. NSE was measured at the same time-point. Among the 673 microRNAs detected, brain-enriched miR9-3p, miR124-3p and miR129-5p positively correlated with NSE levels (all p < 0.001). Interestingly, these correlations were absent when only the good outcome group was analyzed (p > 0.5). Moreover, these correlations were unaffected by demographic and clinical characteristics. All three microRNAs predicted neurological outcome at 6 months. Circulating levels of brain-enriched microRNAs are correlated with NSE levels and hence can reflect the extent of brain injury in patients after CA. This observation strengthens the potential of brain-enriched microRNAs to aid in outcome prognostication after CA. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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16 pages, 5207 KiB

Open AccessArticle

Myostatin Inhibits Vascular Smooth Muscle Cell Proliferation and Local 14q32 microRNA Expression, But Not Systemic Inflammation or Restenosis

by Eveline A.C. Goossens, Margreet R. de Vries, J. Wouter Jukema, Paul H.A. Quax and A. Yaël Nossent

Int. J. Mol. Sci. 2020, 21(10), 3508; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21103508 - 15 May 2020

Cited by 13 | Viewed by 3031

Abstract

Myostatin is a negative regulator of muscle cell growth and proliferation. Furthermore, myostatin directly affects the expression of 14q32 microRNAs by binding the 14q32 locus. Direct inhibition of 14q32 microRNA miR-495-3p decreased postinterventional restenosis via inhibition of both vascular smooth muscle cell (VSMC) proliferation and local inflammation. Here, we aimed to investigate the effects of myostatin in a mouse model for postinterventional restenosis. In VSMCs in vitro, myostatin led to the dose-specific downregulation of 14q32 microRNAs miR-433-3p, miR-494-3p, and miR-495-3p. VSMC proliferation was inhibited, where cell migration and viability remained unaffected. In a murine postinterventional restenosis model, myostatin infusion did not decrease restenosis, neointimal area, or lumen stenosis. Myostatin inhibited expression of both proliferation marker PCNA and of 14q32 microRNAs miR-433-3p, miR-494-3p, and miR-495-3p dose-specifically in cuffed femoral arteries. However, 14q32 microRNA expression remained unaffected in macrophages and macrophage activation as well as macrophage influx into lesions were not decreased. In conclusion, myostatin did not affect postinterventional restenosis. Although myostatin inhibits 14q32 microRNA expression and proliferation in VSMCs, myostatin had no effect on macrophage activation and infiltration. Our findings underline that restenosis is driven by both VSMC proliferation and local inflammation. Targeting only one of these components is insufficient to prevent restenosis. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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Review

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27 pages, 1170 KiB

Open AccessReview

Non-Coding RNAs in the Brain-Heart Axis: The Case of Parkinson’s Disease

by Shubhra Acharya, Antonio Salgado-Somoza, Francesca Maria Stefanizzi, Andrew I. Lumley, Lu Zhang, Enrico Glaab, Patrick May and Yvan Devaux

Int. J. Mol. Sci. 2020, 21(18), 6513; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186513 - 06 Sep 2020

Cited by 19 | Viewed by 5993

Abstract

Parkinson’s disease (PD) is a complex and heterogeneous disorder involving multiple genetic and environmental influences. Although a wide range of PD risk factors and clinical markers for the symptomatic motor stage of the disease have been identified, there are still no reliable biomarkers available for the early pre-motor phase of PD and for predicting disease progression. High-throughput RNA-based biomarker profiling and modeling may provide a means to exploit the joint information content from a multitude of markers to derive diagnostic and prognostic signatures. In the field of PD biomarker research, currently, no clinically validated RNA-based biomarker models are available, but previous studies reported several significantly disease-associated changes in RNA abundances and activities in multiple human tissues and body fluids. Here, we review the current knowledge of the regulation and function of non-coding RNAs in PD, focusing on microRNAs, long non-coding RNAs, and circular RNAs. Since there is growing evidence for functional interactions between the heart and the brain, we discuss the benefits of studying the role of non-coding RNAs in organ interactions when deciphering the complex regulatory networks involved in PD progression. We finally review important concepts of harmonization and curation of high throughput datasets, and we discuss the potential of systems biomedicine to derive and evaluate RNA biomarker signatures from high-throughput expression data. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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31 pages, 1817 KiB

Open AccessReview

Approaching Sex Differences in Cardiovascular Non-Coding RNA Research

by Amela Jusic, Antonio Salgado-Somoza, Ana B. Paes, Francesca Maria Stefanizzi, Núria Martínez-Alarcón, Florence Pinet, Fabio Martelli, Yvan Devaux, Emma Louise Robinson and Susana Novella

Int. J. Mol. Sci. 2020, 21(14), 4890; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144890 - 10 Jul 2020

Cited by 14 | Viewed by 4501

Abstract

Cardiovascular disease (CVD) is the biggest cause of sickness and mortality worldwide in both males and females. Clinical statistics demonstrate clear sex differences in risk, prevalence, mortality rates, and response to treatment for different entities of CVD. The reason for this remains poorly understood. Non-coding RNAs (ncRNAs) are emerging as key mediators and biomarkers of CVD. Similarly, current knowledge on differential regulation, expression, and pathology-associated function of ncRNAs between sexes is minimal. Here, we provide a state-of-the-art overview of what is known on sex differences in ncRNA research in CVD as well as discussing the contributing biological factors to this sex dimorphism including genetic and epigenetic factors and sex hormone regulation of transcription. We then focus on the experimental models of CVD and their use in translational ncRNA research in the cardiovascular field. In particular, we want to highlight the importance of considering sex of the cellular and pre-clinical models in clinical studies in ncRNA research and to carefully consider the appropriate experimental models most applicable to human patient populations. Moreover, we aim to identify sex-specific targets for treatment and diagnosis for the biggest socioeconomic health problem globally. Full article

(This article belongs to the Special Issue RNAs in Brain and Heart Diseases - EU-CardioRNA COST Action)

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