Publications
10 results found
King O, Cruz-Moreira D, Sayed A, et al., 2022, Functional microvascularization of human myocardium in vitro, Cell Reports: Methods, Vol: 2, Pages: 1-16, ISSN: 2667-2375
In this study, we report static and perfused models of human myocardial-microvascular interaction. In static culture, we observe distinct regulation of electrophysiology of human induced pluripotent stem cell derived-cardiomyocytes (hiPSC-CMs) in co-culture with human cardiac microvascular endothelial cells (hCMVECs) and human left ventricular fibroblasts (hLVFBs), including modification of beating rate, action potential, calcium handling, and pro-arrhythmic substrate. Within a heart-on-a-chip model, we subject this three-dimensional (3D) co-culture to microfluidic perfusion and vasculogenic growth factors to induce spontaneous assembly of perfusable myocardial microvasculature. Live imaging of red blood cells within myocardial microvasculature reveals pulsatile flow generated by beating hiPSC-CMs. This study therefore demonstrates a functionally vascularized in vitro model of human myocardium with widespread potential applications in basic and translational research.
Couch LS, Fiedler J, Chick G, et al., 2022, Circulating microRNAs predispose to takotsubo syndrome following high-dose adrenaline exposure, Cardiovascular Research, Vol: 118, Pages: 1758-1770, ISSN: 0008-6363
AIMS: Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress. It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and absence of coronary occlusion. We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS. METHODS AND RESULTS: miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus. Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed. Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS. In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal) cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity. They also enhanced the initial positive inotropic effect of adrenaline in basal cells. Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes. Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavβ subunit), RGS4 (regulator of G-protein signalling 4) and G-protein subunit Gβ (GNB1) as underlying these effects. CONCLUSION: miR-16 and miR-26a sensitise the heart to TTS-like changes produced by adrenaline. Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future. TRANSLATIONAL PERSPECTIVE: TTS-associated miRs have the potential to be active players predisposing to TTS. Feasibly, their measurement in recovered TTS patients during subsequent peri
Woollard K, 2022, Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages, BMC Nephrology, Vol: 23, Pages: 1-15, ISSN: 1471-2369
Background – The leading cause of death in end-stage kidney disease is related tocardiovascular disease. Macrophages are known to be involved in both chronic kidney disease(CKD) and heart failure, however their role in the development of cardiorenal syndrome is lessclear. We thus sought to investigate the role of macrophages in uremic cardiac disease.Methods – We assessed cardiac response in two experimental models of CKD and testedmacrophage and chemokine implication in monocytopenic CCR2-/- and anti-CXCL10 treatedmice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSCderived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors. Results– We found that reduced kidney function resulted in the expansion of cardiac macrophages,in particular through local proliferation of resident populations. Influx of circulating monocytescontributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophageexpansion in uremic disease. In humans, we found increased plasma CXCL10 concentrationsin advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiacfibroblasts. Conclusions – This study provides new insight into the role of the innate immunesystem in uremic cardiomyopathy.
King O, Cruz-Moreira D, Kit-Anan W, et al., 2020, Influence of perfusable microvasculature on excitation-contraction coupling in IPSC-derived myocardium, European-Society-of-Cardiology (ESC) Congress, Publisher: OXFORD UNIV PRESS, Pages: 3590-3590, ISSN: 0195-668X
King O, Cruz-Moreira D, Kermani F, et al., 2020, NON-MYOCYTE INFLUENCE ON EXCITATION-CONTRACTION COUPLING IN INDUCED PLURIPOTENT STEM CELL DERIVED MYOCARDIUM, Publisher: SPRINGER, Pages: 272-272, ISSN: 0920-3206
King O, Cruz-Moreira D, Kit-Anan SW, et al., 2020, Vascularized Myocardium-On-A-Chip: Excitation-Contraction Coupling in Perfused Cardiac Co-Cultures, 64th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 410A-410A, ISSN: 0006-3495
Fourre JD, Bardi I, King O, et al., 2019, Endothelial cell activation by pro-inflammatory cytokines exerts novel paracrine effects on cocultured cardiomyocytes, Publisher: WILEY, Pages: 91-91, ISSN: 1748-1708
Fourre J, Bardi I, Maughan RT, et al., 2019, Endothelial cell activation by pro-inflammatory cytokines exerts novel paracrine effects on co-cultured cardiomyocytes, Congress of the European-Society-of-Cardiology (ESC) / World Congress of Cardiology, Publisher: OXFORD UNIV PRESS, Pages: 3904-3904, ISSN: 0195-668X
King O, Kermani F, Wang B, et al., 2019, Endothelial Cell Regulation of Excitation-Contraction Coupling in Induced Pluripotent Stem Cell Derived Myocardium, 63rd Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 153A-153A, ISSN: 0006-3495
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Fourre J, Terracciano C, Mason J, 2019, Endothelial Cells Exert Stimulus-Specific Paracrine Effects on Co-Cultured Cardiomyocytes During Inflammation, 3rd Joint Meeting of the European-Society-for-Microcirculation (ESM) and the European-Vascular-Biology-Organization (EVBO), Publisher: KARGER, Pages: 35-35, ISSN: 1018-1172
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