228 results found
Harries I, Biglino G, Ford K, et al., 2022, Prospective multiparametric CMR characterization and MicroRNA profiling of anthracycline cardiotoxicity: A pilot translational study., Int J Cardiol Heart Vasc, Vol: 43, ISSN: 2352-9067
Background: Anthracycline cardiotoxicity is a significant clinical challenge. Biomarkers to improve risk stratification and identify early cardiac injury are required. Objectives: The purpose of this pilot study was to prospectively characterize anthracycline cardiotoxicity using cardiovascular magnetic resonance (CMR), echocardiography and MicroRNAs (MiRNAs), and identify baseline predictors of LVEF recovery. Methods: Twenty-four patients (age 56 range 18-75 years; 42 % female) with haematological malignancy scheduled to receive anthracycline chemotherapy (median dose 272 mg/m2 doxorubicin equivalent) were recruited and evaluated at three timepoints (baseline, completion of chemotherapy, and 6 months after completion of chemotherapy) with multiparametric 1.5 T CMR, echocardiography and circulating miRNAs sequencing. Results: Seventeen complete datasets were obtained. CMR left ventricular ejection fraction (LVEF) fell significantly between baseline and completion of chemotherapy (61 ± 3 vs 53 ± 3 %, p < 0.001), before recovering significantly at 6-month follow-up (55 ± 3 %, p = 0.018). Similar results were observed for 3D echocardiography-derived LVEF and CMR-derived longitudinal, circumferential and radial feature-tracking strain. Patients were divided into tertiles according to LVEF recovery (poor recovery, partial recovery, good recovery). CMR-derived mitral annular plane systolic excursion (MAPSE) was significantly different at baseline in patients exhibiting poor LVEF recovery (11.7 ± 1.5 mm) in comparison to partial recovery (13.7 ± 2.7 mm), and good recovery (15.7 ± 3.1 mm; p = 0.028). Furthermore, baseline miRNA-181-5p and miRNA-221-3p expression were significantly higher in this group. T2 mapping increased significantly on completion of chemotherapy compared to baseline (54.0
Ji J, Anwar M, Petretto E, et al., 2022, PPMS: a framework to profile primary microRNAs from single-cell RNA-sequencing datasets, Briefings in Bioinformatics, ISSN: 1467-5463
Motivation:Single-cell/nuclei RNA sequencing (scRNA-seq) technologies can simultaneously quantify gene expression in thousands of cells across the genome. However, the majority of the non-coding RNAs, such as microRNAs (miRNAs), cannot currently be profiled at the same scale. MiRNAs are a class of small non-coding RNAs and play an important role in gene regulation. MiRNAs originate from the processing of primary transcripts, known as primary-microRNAs (pri-miRNAs). The pri-miRNA transcripts, independent of their cognate miRNAs, can also function as long non-coding RNAs, code for micropeptides or even interact with DNA, acting like enhancers. Therefore, it is apparent that the significance of scRNA-seq pri-miRNA profiling expands beyond using pri-miRNA as proxies of mature miRNAs. However, there are no computational methods that allow profiling and quantification of pri-miRNAs at the single-cell type resolution.Results:We have developed a simple yet effective computational framework to Profile Pri-MiRNAs from Single-cell RNA-sequencing datasets (PPMS). Based on user input, PPMS can profile pri-miRNAs at cell-type resolution. PPMS can be applied to both newly produced and publicly available datasets obtained via single cell or single nuclei RNA-seq. It allows users to (i) investigate the distribution of pri-miRNAs across cell types and cell states and (ii) establish a relationship between the number of cells/reads sequenced and the detection of pri-miRNAs. Here, to demonstrate its efficacy, we have applied PPMS to publicly available scRNA-seq data generated from (a) individual chambers (ventricles and atria) of the human heart, (b) human pluripotent stem cells during their differentiation into cardiomyocytes (the heart beating cells) and (c) hiPSCs-derived cardiomyocytes infected with SARS-CoV2 virus. Availability and implementation:PPMS is free to use under a GNU license and is available to download from (GitHub link: https://github.com/SrivastavaLab-ICL/PPMS)
Skeffington KL, Moscarelli M, Abdul-Ghani S, et al., 2022, Pathology-related changes in cardiac energy metabolites, inflammatory response and reperfusion injury following cardioplegic arrest in patients undergoing open-heart surgery, FRONTIERS IN CARDIOVASCULAR MEDICINE, Vol: 9, ISSN: 2297-055X
Abdul-Ghani S, Skeffington KL, Kim M, et al., 2022, Effect of cardioplegic arrest and reperfusion on left and right ventricular proteome/phosphoproteome in patients undergoing surgery for coronary or aortic valve disease, INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, Vol: 49, ISSN: 1107-3756
Davidson SM, Boulanger CM, Aikawa E, et al., 2022, Methods for the identification and characterization of extracellular vesicles in cardiovascular studies: from exosomes to microvesicles, CARDIOVASCULAR RESEARCH, ISSN: 0008-6363
Ben-Aicha S, Buchanan J, Punjabi P, et al., 2022, Efficacy of treatments tested in COVID-19 patients with cardiovascular disease. A meta-analysis, PERFUSION-UK, ISSN: 0267-6591
Posadino AM, Erre GL, Cossu A, et al., 2022, NADPH-derived ROS generation drives fibrosis and endothelial-to-mesenchymal transition in systemic sclerosis: Potential cross talk with circulating miRNAs., Biomol Concepts, Vol: 13, Pages: 11-24
Systemic sclerosis (SSc) is an immune disorder characterized by diffuse fibrosis and vascular abnormalities of the affected organs. Although the etiopathology of this disease is largely unknown, endothelial damage and oxidative stress appear implicated in its initiation and maintenance. Here, we show for the first time that circulating factors present in SSc sera increased reactive oxygen species (ROS) production, collagen synthesis, and proliferation of human pulmonary microvascular endothelial cells (HPMECs). The observed phenomena were also associated with endothelial to mesenchymal transition (EndMT) as indicated by decreased von Willebrand factor (vWF) expression and increased alpha-smooth muscle actin, respectively, an endothelial and mesenchymal marker. SSc-induced fibroproliferative effects were prevented by HPMECs exposition to the NADPH oxidase inhibitor diphenyleneiodonium, demonstrating ROS's causative role and suggesting their cellular origin. Sera from SSc patients showed significant changes in the expression of a set of fibrosis/EndMT-associated microRNAs (miRNA), including miR-21, miR-92a, miR-24, miR-27b, miR-125b, miR-29c, and miR-181b, which resulted significantly upregulated as compared to healthy donors sera. However, miR29b resulted downregulated in SSc sera, whereas no significant differences were found in the expression of miR-29a in the two experimental groups of samples. Taking together our data indicate NADPH oxidase-induced EndMT as a potential mechanism of SSc-associated fibrosis, suggesting fibrosis-associated miRNAs as potentially responsible for initiating and sustaining the vascular alterations observed in this pathological condition.
Abdulrazzak H, Ruiz-Lozano P, Emanueli C, 2022, Epicardium-derived extracellular vesicles: a promising avenue for cardiac regeneration, CARDIOVASCULAR RESEARCH, Vol: 118, Pages: 350-352, ISSN: 0008-6363
Robinson EL, Emanueli C, Martelli F, et al., 2021, Leveraging non-coding RNAs to fight cardiovascular disease: the EU-CardioRNA network, EUROPEAN HEART JOURNAL, Vol: 42, Pages: 4881-4883, ISSN: 0195-668X
Floriano JF, Emanueli C, Vega S, et al., 2021, Pro-angiogenic approach for skeletal muscle regeneration, BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS, Vol: 1866, ISSN: 0304-4165
Vanhaverbeke M, Attard R, Bartekova M, et al., 2021, Peripheral blood RNA biomarkers for cardiovascular disease from bench to bedside: a position paper from the EU-CardioRNA COST action CA17129, CARDIOVASCULAR RESEARCH, ISSN: 0008-6363
Scott A, Ballesteros LS, Bradshaw M, et al., 2021, In Vivo Characterization of Endogenous Cardiovascular Extracellular Vesicles in Larval and Adult Zebrafish, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 41, Pages: 2454-2468, ISSN: 1079-5642
Abdulrazzak H, Ruiz-Lozano P, Emanueli C, 2021, Epicardium-derived extracellular vesicles: a promising avenue for cardiac regeneration (vol 118, pg 350, 2022), CARDIOVASCULAR RESEARCH, Vol: 118, Pages: 1611-1611, ISSN: 0008-6363
Robinson EL, Baker AH, Brittan M, et al., 2021, Dissecting the transcriptome in cardiovascular disease, CARDIOVASCULAR RESEARCH, Vol: 118, Pages: 1004-1019, ISSN: 0008-6363
Sweaad WK, Stefanizzi FM, Chamorro-Jorganes A, et al., 2021, Relevance of N6-methyladenosine regulators for transcriptome: Implications for development and the cardiovascular system, JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, Vol: 160, Pages: 56-70, ISSN: 0022-2828
Aday S, Hazan-Halevy I, Chamorro-Jorganes A, et al., 2021, Bioinspired artificial exosomes based on lipid nanoparticles carrying let-7b-5p promote angiogenesis in vitro and in vivo, Molecular Therapy, Vol: 29, Pages: 2239-2252, ISSN: 1525-0016
MicroRNAs (miRNAs) regulate gene expression by post-transcriptional inhibition of target genes. Proangiogenic small extracellular vesicles (sEVs; popularly identified with the name "exosomes") with a composite cargo of miRNAs are secreted by cultured stem cells and present in human biological fluids. Lipid nanoparticles (LNPs) represent an advanced platform for clinically approved delivery of RNA therapeutics. In this study, we aimed to (1) identify the miRNAs responsible for sEV-induced angiogenesis; (2) develop the prototype of bioinspired "artificial exosomes" (AEs) combining LNPs with a proangiogenic miRNA, and (3) validate the angiogenic potential of the bioinspired AEs. We previously reported that human sEVs from bone marrow (BM)-CD34+ cells and pericardial fluid (PF) are proangiogenic. Here, we have shown that sEVs secreted from saphenous vein pericytes and BM mesenchymal stem cells also promote angiogenesis. Analysis of miRNA datasets available in-house or datamined from GEO identified the let-7 family as common miRNA signature of the proangiogenic sEVs. LNPs with either hsa-let-7b-5p or cyanine 5 (Cy5)-conjugated Caenorhabditis elegans miR-39 (Cy5-cel-miR-39; control miRNA) were prepared using microfluidic micromixing. let-7b-5p-AEs did not cause toxicity and transferred functionally active let-7b-5p to recipient endothelial cells (ECs). let-7b-AEs also improved EC survival under hypoxia and angiogenesis in vitro and in vivo. Bioinspired proangiogenic AEs could be further developed into innovative nanomedicine products targeting ischemic diseases.
Chamorro-Jorganes A, Sweaad WK, Katare R, et al., 2021, METTL3 Regulates Angiogenesis by Modulating let-7e-5p and miRNA-18a-5p Expression in Endothelial Cells, ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, Vol: 41, Pages: E325-E337, ISSN: 1079-5642
Badimon L, Robinson EL, Jusic A, et al., 2021, Cardiovascular RNA markers and artificial intelligence may improve COVID-19 outcome: a position paper from the EU-CardioRNA COST Action CA17129, CARDIOVASCULAR RESEARCH, Vol: 117, Pages: 1823-1840, ISSN: 0008-6363
Bollini S, Emanueli C, 2021, To serve and protect: a new heart patrolling and recycling role for macrophages, CARDIOVASCULAR RESEARCH, Vol: 117, Pages: E17-E20, ISSN: 0008-6363
Moscarelli M, Angelini GD, Emanueli C, et al., 2021, Remote ischemic preconditioning in isolated valve intervention. A pooled meta-analysis, INTERNATIONAL JOURNAL OF CARDIOLOGY, Vol: 324, Pages: 146-151, ISSN: 0167-5273
Greco S, Made A, Gaetano C, et al., 2020, Noncoding RNAs implication in cardiovascular diseases in the COVID-19 era, JOURNAL OF TRANSLATIONAL MEDICINE, Vol: 18
Spencer HL, Sanders R, Boulberdaa M, et al., 2020, The LINC00961 transcript and its encoded micropeptide, small regulatory polypeptide of amino acid response, regulate endothelial cell function, CARDIOVASCULAR RESEARCH, Vol: 116, Pages: 1981-1994, ISSN: 0008-6363
de Abreu RC, Fernandes H, Martins PADC, et al., 2020, Native and bioengineered extracellular vesicles for cardiovascular therapeutics, NATURE REVIEWS CARDIOLOGY, Vol: 17, Pages: 685-697, ISSN: 1759-5002
Robinson EL, Gomes CPC, Potocnjak I, et al., 2020, A Year in the Life of the EU-CardioRNA COST Action: CA17129 Catalysing Transcriptomics Research in Cardiovascular Disease, NON-CODING RNA, Vol: 6
Shearn AIU, Aday S, Ben-Aicha S, et al., 2020, Analysis of neat biofluids obtained during cardiac surgery using nanoparticle tracking analysis: methodological considerations, Frontiers in Cell and Developmental Biology, Vol: 8, Pages: 1-14, ISSN: 2296-634X
Small extracellular vesicles (sEVs) are those nanovesicles 30–150 nm in size with a role in cell signalling and potential as biomarkers of disease. Nanoparticle tracking analysis (NTA) techniques are commonly used to measure sEV concentration in biofluids. However, this quantification technique can be susceptible to sample handing and machine settings. Moreover, some classes of lipoproteins are of similar sizes and could therefore confound sEV quantification, particularly in blood-derived preparations, such serum and plasma. Here we have provided methodological information on NTA measurements and systematically investigated potential factors that could interfere with the reliability and repeatability of results obtained when looking at neat biofluids (i.e., human serum and pericardial fluid) obtained from patients undergoing cardiac surgery and from healthy controls. Data suggest that variables that can affect vesicle quantification include the level of contamination from lipoproteins, number of sample freeze/thaw cycles, sample filtration, using saline-based diluents, video length and keeping the number of particles per frame within defined limits. Those parameters that are of less concern include focus, the “Maximum Jump” setting and the number of videos recorded. However, if these settings are clearly inappropriate the results obtained will be spurious. Similarly, good experimental practice suggests that multiple videos should be recorded. In conclusion, NTA is a perfectible, but still commonly used system for sEVs analyses. Provided users handle their samples with a highly robust and consistent protocol, and accurately report these aspects, they can obtain data that could potentially translate into new clinical biomarkers for diagnosis and monitoring of cardiovascular disease.
Emanueli C, Badimon L, Martelli F, et al., 2020, Call to action for the cardiovascular side of COVID-19 A call for cooperative action from the EU-CardioRNA COST Action, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 1796-1797, ISSN: 0195-668X
Ozaki Tan SJ, Floriano JF, Nicastro L, et al., 2020, Novel Applications of Mesenchymal Stem Cell-Derived Exosomes for Myocardial Infarction Therapeutics, BIOMOLECULES, Vol: 10
Stoica SC, Dorobantu DM, Vardeu A, et al., 2020, MicroRNAs as potential biomarkers in congenital heart surgery, JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY, Vol: 159, Pages: 1532-+, ISSN: 0022-5223
Tikhomirov R, Donnell BR-O, Catapano F, et al., 2020, Exosomes: From potential culprits to new therapeutic promise in the setting of cardiac fibrosis, Cells, Vol: 9, ISSN: 2073-4409
Fibrosis is a significant global health problem associated with many inflammatory and degenerative diseases affecting multiple organs, individually or simultaneously. Fibrosis develops when extracellular matrix (ECM) remodeling becomes excessive or uncontrolled and is associated with nearly all forms of heart disease. Cardiac fibroblasts and myofibroblasts are the main effectors of ECM deposition and scar formation. The heart is a complex multicellular organ, where the various resident cell types communicate between themselves and with cells of the blood and immune systems. Exosomes, which are small extracellular vesicles, (EVs), contribute to cell-to-cell communication and their pathophysiological relevance and therapeutic potential is emerging. Here, we will critically review the role of endogenous exosomes as possible fibrosis mediators and discuss the possibility of using stem cell-derived and/or engineered exosomes as anti-fibrotic agents.
Marchetti M, Meloni M, Anwar M, et al., 2020, MicroRNA-24-3p Targets Notch and Other Vascular Morphogens to Regulate Post-ischemic Microvascular Responses in Limb Muscles, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 21
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