Publications
223 results found
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., Int J Mol Med, Vol: 49
Our earlier work has shown inter‑disease and intra‑disease differences in the cardiac proteome between right (RV) and left (LV) ventricles of patients with aortic valve stenosis (AVS) or coronary artery disease (CAD). Whether disease remodeling also affects acute changes occuring in the proteome during surgical intervention is unknown. This study investigated the effects of cardioplegic arrest on cardiac proteins/phosphoproteins in LV and RV of CAD (n=6) and AVS (n=6) patients undergoing cardiac surgery. LV and RV biopsies were collected during surgery before ischemic cold blood cardioplegic arrest (pre) and 20 min after reperfusion (post). Tissues were snap frozen, proteins extracted, and the extracts were used for proteomic and phosphoproteomic analysis using Tandem Mass Tag (TMT) analysis. The results were analysed using QuickGO and Ingenuity Pathway Analysis softwares. For each comparision, our proteomic analysis identified more than 3,000 proteins which could be detected in both the pre and Post samples. Cardioplegic arrest and reperfusion were associated with significant differential expression of 24 (LV) and 120 (RV) proteins in the CAD patients, which were linked to mitochondrial function, inflammation and cardiac contraction. By contrast, AVS patients showed differential expression of only 3 LV proteins and 2 RV proteins, despite a significantly longer duration of ischaemic cardioplegic arrest. The relative expression of 41 phosphoproteins was significantly altered in CAD patients, with 18 phosphoproteins showing altered expression in AVS patients. Inflammatory pathways were implicated in the changes in phosphoprotein expression in both groups. Inter‑disease comparison for the same ventricular chamber at both timepoints revealed differences relating to inflammation and adrenergic and calcium signalling. In conclusion, the present study found that ischemic arrest and reperfusion trigger different changes in t
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
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- Citations: 1
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
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- Citations: 1
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
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- Citations: 2
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
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- Citations: 7
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.
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
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
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- Citations: 5
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
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- Citations: 3
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
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- Citations: 2
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
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- Citations: 1
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
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- Citations: 1
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
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- Citations: 7
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
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- Citations: 58
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
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- Citations: 2
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 COSTAction, EUROPEAN HEART JOURNAL, Vol: 41, Pages: 1796-1797, ISSN: 0195-668X
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- Citations: 10
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
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- Citations: 27
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
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- Citations: 5
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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- Citations: 9
Floriano JF, Willis G, Catapano F, et al., 2020, Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus, CELLS, Vol: 9
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- Citations: 9
Gomes CPDC, Schroen B, Kuster GM, et al., 2020, Regulatory RNAs in Heart Failure, CIRCULATION, Vol: 141, Pages: 313-328, ISSN: 0009-7322
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- Citations: 63
Vesentini G, Barbosa AMP, Damasceno DC, et al., 2020, Alterations in the structural characteristics of rectus abdominis muscles caused by diabetes and pregnancy: A comparative study of the rat model and women., PLoS One, Vol: 15
BACKGROUND AND OBJECTIVE: In the present study, we compared the effect of diabetic pregnancy on the rectus abdominis muscle (RAM) in humans and rats. We hypothesized that our animal model could provide valuable information about alterations in the RAM of women with Gestational Diabetes (GDM). METHOD: Newborns female rats (n = 10/group) were administered streptozotocin (100 mg/kg body weight) subcutaneously and were mated on reaching adulthood, to develop the mild hyperglycemic pregnant (MHP) rat model. At the end of pregnancy, the mothers were sacrificed, and the RAM tissue was collected. Pregnant women without GDM (non-GDM group; n = 10) and those diagnosed with GDM (GDM group; n = 8) and undergoing treatment were recruited, and RAM samples were obtained at C-section. The RAM architecture and the distribution of the fast and slow fibers and collagen were studied by immunohistochemistry. RESULTS: No statistically significant differences in the maternal and fetal characters were observed between the groups in both rats and women. However, significant changes in RAM architecture were observed. Diabetes in pregnancy increased the abundance of slow fibers and decreased fast fiber number and area in both rats and women. A decrease in collagen distribution was observed in GDM women; however, a similar change was not observed in the MHP rats. CONCLUSION: Our results indicated that pregnancy- associated diabetes- induced similar structural adaptations in the RAM of women and rats with slight alterations in fiber type number and area. These findings suggest that the MHP rat model can be used for studying the effects of pregnancy-associated diabetes on the fiber structure of RAM.
Chamorro-Jorganes A, Anwar M, Emanueli C, 2019, Changes in HDL-microRNA might create a lasting memory of high-fat diet, Cardiovascular Research, Vol: 116, Pages: 1237-1239, ISSN: 0008-6363
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