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https://www.readbyqxmd.com/read/29184625/confounding-factors-in-vesicle-uptake-studies-using-fluorescent-lipophilic-membrane-dyes
#1
Kaloyan Takov, Derek M Yellon, Sean M Davidson
Small extracellular vesicles (sEVs) such as exosomes are nanocarriers of proteins, RNAs and DNAs. Isolation of pure sEV populations remains challenging, with reports of protein and lipoprotein contaminants in the isolates. Cellular uptake - a cornerstone for understanding exosome and sEV function - is frequently examined using lipophilic dyes such as PKH67 or CellMask to label the vesicles. In this study, we investigated whether contaminants can confound the outcomes from sEV and exosomes uptake experiments...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29169473/xenon-a-noble-member-of-the-cardioprotection-club
#2
EDITORIAL
Derek M Yellon, Xavier Rossello
No abstract text is available yet for this article.
November 28, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/29159980/role-of-pi3k-in-myocardial-ischaemic-preconditioning-mapping-pro-survival-cascades-at-the-trigger-phase-and-at-reperfusion
#3
Xavier Rossello, Jaime A Riquelme, Sean M Davidson, Derek M Yellon
The Reperfusion Injury Salvage Kinase (RISK) pathway is considered the main pro-survival kinase cascade mediating the ischaemic preconditioning (IPC) cardioprotective effect. To assess the role of PI3K-Akt, its negative regulator PTEN and other pro-survival proteins such as ERK and STAT3 in the context of IPC, C57BL/6 mouse hearts were retrogradely perfused in a Langendorff system and subjected to 4 cycles of 5 min. ischaemia and 5 min. reperfusion prior to 35 min. of global ischaemia and 120 min. of reperfusion...
November 20, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29143177/the-risk-pathway-and-beyond
#4
REVIEW
Xavier Rossello, Derek M Yellon
Research on cardioprotection has attracted considerable attention during the past 30 years following the discovery of ischemic preconditioning with great advances being made in the field, particularly in the description of the molecular signalling behind this cardioprotective intervention. In a time when basic research is struggling to translate its findings into therapies in the clinical setting, this viewpoint has the intention of presenting to clinical and basic scientists how the reperfusion injury salvage kinase pathway has been described and dissected, as well as highlighting its relevance in cardioprotection...
November 15, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29122678/exosomes-and-cardioprotection-a-critical-analysis
#5
REVIEW
Sean M Davidson, Derek M Yellon
Exosomes are nano-sized vesicles released by numerous cell types that appear to have diverse beneficial effects on the injured heart. Studies using exosomes from stem cells or from the blood have indicated that they are able to protect the heart both in models of acute ischaemia and reperfusion, and during chronic ischaemia. In addition to decreasing initial infarct size, they are able to stimulate angiogenesis, reduce fibrosis and remodelling, alter immune cell function and improve long-term cardiac contractile function...
November 6, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29043508/the-role-of-pi3k%C3%AE-isoform-in-cardioprotection
#6
Xavier Rossello, Jaime A Riquelme, Zhenhe He, Stasa Taferner, Bart Vanhaesebroeck, Sean M Davidson, Derek M Yellon
Ischemic preconditioning (IPC) limits myocardial infarct size through the activation of the PI3K-Akt signal cascade; however, little is known about the roles of individual PI3K isoforms in cardioprotection. We aimed, therefore, to elucidate the role of the PI3Kα isoform in cardioprotection Pharmacological PI3Kα inhibition was assessed in isolated-perfused mouse hearts subjected to ischemia/reperfusion injury (IRI), either during the IPC procedure or at reperfusion. PI3Kα inhibition abrogated the IPC-induced protective effect at reperfusion, but not when given only during the IPC protocol...
October 17, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29040423/title-therapeutic-strategies-utilising-sdf-1%C3%AE-in-ischaemic-cardiomyopathy
#7
Oliver J Ziff, Daniel I Bromage, Derek M Yellon, Sean M Davidson
Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilise and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium...
October 13, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29030201/sglt2-inhibitors-hypotheses-on-the-mechanism-of-cardiovascular-protection
#8
Robert M Bell, Derek M Yellon
No abstract text is available yet for this article.
October 10, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28904083/assessing-the-effects-of-mitofusin-2-deficiency-in-the-adult-heart-using-3d-electron-tomography
#9
Siavash Beikoghli Kalkhoran, Andrew R Hall, Ian J White, Jackie Cooper, Qiao Fan, Sang-Bing Ong, Sauri Hernández-Reséndiz, Hector Cabrera-Fuentes, Kroekkiat Chinda, Bibhas Chakraborty, Gerald W Dorn, Derek M Yellon, Derek J Hausenloy
The effects of mitofusin 2 (MFN2) deficiency, on mitochondrial morphology and the mitochondria-junctional sarcoplasmic reticulum (jSR) complex in the adult heart, have been previously investigated using 2D electron microscopy, an approach which is unable to provide a 3D spatial assessment of these imaging parameters. Here, we use 3D electron tomography to show that MFN2-deficient mitochondria are larger in volume, more elongated, and less rounded; have fewer mitochondria-jSR contacts, and an increase in the distance between mitochondria and jSR, when compared to WT mitochondria...
September 2017: Physiological Reports
https://www.readbyqxmd.com/read/28874421/combination-therapy-to-target-reperfusion-injury-after-st-segment-elevation-myocardial-infarction-a-more-effective-approach-to-cardioprotection
#10
EDITORIAL
Derek J Hausenloy, Derek M Yellon
No abstract text is available yet for this article.
September 5, 2017: Circulation
https://www.readbyqxmd.com/read/28859295/melatonin-as-a-cardioprotective-therapy-following-st-segment-elevation-myocardial-infarction-is-it-really-promising-reply
#11
Derek J Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M Davidson, James Downey, Felix B Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P G Sluijter, Linda W Van Laake, Jakob Vinten-Johansen, Derek M Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
No abstract text is available yet for this article.
September 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28840975/cardioprotection-mediated-by-exosomes-is-impaired-in-the-setting-of-type-ii-diabetes-but-can-be-rescued-by-the-use-of-non-diabetic-exosomes-in-vitro
#12
Sean M Davidson, Jaime A Riquelme, Kaloyan Takov, Jose M Vicencio, Claire Boi-Doku, Vanessa Khoo, Christian Doreth, Dina Radenkovic, Sergio Lavandero, Derek M Yellon
Many patients with ischaemic heart disease also have diabetes. As myocardial infarction is a major cause of mortality and morbidity in these patients, treatments that increase cell survival in response to ischaemia and reperfusion are needed. Exosomes-nano-sized, lipid vesicles released from cells-can protect the hearts of non-diabetic rats. We previously showed that exosomal HSP70 activates a cardioprotective signalling pathway in cardiomyocytes culminating in ERK1/2 and HSP27 phosphorylation. Here, we investigated whether the exosomal cardioprotective pathway remains intact in the setting of type II diabetes...
August 25, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28794136/neutrophil-gelatinase-associated-lipocalin-prior-to-cardiac-surgery-predicts-acute-kidney-injury-and-mortality
#13
Heerajnarain Bulluck, Raju Maiti, Bibhas Chakraborty, Luciano Candilio, Tim Clayton, Richard Evans, David P Jenkins, Shyam Kolvekar, Gudrun Kunst, Christopher Laing, Jennifer Nicholas, John Pepper, Derek M Yellon, Derek J Hausenloy
OBJECTIVE: We aimed to investigate whether preoperative serum neutrophil gelatinase-associated lipocalin (sNGALpre-op) predicted postoperative acute kidney injury (AKI) during hospitalisation and 1-year cardiovascular and all-cause mortality following adult cardiac surgery. METHODS: This study was a post hoc analysis of the Effect of Remote Ischemic Preconditioning on Clinical Outcomes in Patient Undergoing Coronary Artery Bypass Graft Surgery trial involving adult patients undergoing coronary artery bypass graft...
August 9, 2017: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/28736742/unique-morphological-characteristics-of-mitochondrial-subtypes-in-the-heart-the-effect-of-ischemia-and-ischemic-preconditioning
#14
Siavash Beikoghli Kalkhoran, Peter Munro, Fan Qiao, Sang-Bing Ong, Andrew R Hall, Hector Cabrera-Fuentes, Bibhas Chakraborty, William A Boisvert, Derek M Yellon, Derek J Hausenloy
RATIONALE: Three subsets of mitochondria have been described in adult cardiomyocytes - intermyofibrillar (IMF), subsarcolemmal (SSM), and perinuclear (PN). They have been shown to differ in physiology, but whether they also vary in morphological characteristics is unknown. Ischemic preconditioning (IPC) is known to prevent mitochondrial dysfunction induced by acute myocardial ischemia/reperfusion injury (IRI), but whether IPC can also modulate mitochondrial morphology is not known. AIMS: Morphological characteristics of three different subsets of adult cardiac mitochondria along with the effect of ischemia and IPC on mitochondrial morphology will be investigated...
January 2017: Discoveries
https://www.readbyqxmd.com/read/28536472/quantifying-the-area-at-risk-of-myocardial-infarction-in-vivo-using-arterial-spin-labeling-cardiac-magnetic-resonance
#15
Rachel K Dongworth, Adrienne E Campbell-Washburn, Hector A Cabrera-Fuentes, Heerajnarain Bulluck, Thomas Roberts, Anthony N Price, Sauri Hernández-Reséndiz, Roger J Ordidge, David L Thomas, Derek M Yellon, Mark F Lythgoe, Derek J Hausenloy
T2-weighted cardiovascular magnetic resonance (T2-CMR) of myocardial edema can quantify the area-at-risk (AAR) following acute myocardial infarction (AMI), and has been used to assess myocardial salvage by new cardioprotective therapies. However, some of these therapies may reduce edema, leading to an underestimation of the AAR by T2-CMR. Here, we investigated arterial spin labeling (ASL) perfusion CMR as a novel approach to quantify the AAR following AMI. Adult B6sv129-mice were subjected to in vivo left coronary artery ligation for 30 minutes followed by 72 hours reperfusion...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28453734/novel-targets-and-future-strategies-for-acute-cardioprotection-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#16
Derek J Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M Davidson, James Downey, Felix B Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P G Sluijter, Linda W Van Laake, Jakob Vinten-Johansen, Derek M Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury (IRI). During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic-however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing...
May 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28379992/a-novel-recombinant-antibody-specific-to-full-length-stromal-derived-factor-1-for-potential-application-in-biomarker-studies
#17
Daniel I Bromage, Stasa Taferner, Mahesh Pillai, Derek M Yellon, Sean M Davidson
BACKGROUND: Stromal derived factor-1α (SDF-1α/CXCL12) is a chemokine that is up-regulated in diseases characterised by tissue hypoxia, including myocardial infarction, ischaemic cardiomyopathy and remote ischaemic conditioning (RIC), a technique of cyclical, non-injurious ischaemia applied remote from the heart that protects the heat from lethal ischaemia-reperfusion injury. Accordingly, there is considerable interest in SDF-1α as a potential biomarker of such conditions. However, SDF-1α is rapidly degraded and inactivated by dipeptidyl peptidase 4 and other peptidases, and the kinetics of intact SDF-1α remain unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28374972/ventilation-strategy-has-a-major-influence-on-remote-ischaemic-preconditioning-in-mice
#18
Sean M Davidson, Zhenhe He, Alex Dyson, Daniel I Bromage, Derek M Yellon
Whether oxygen should be administered acutely during ST-segment elevation myocardial infarction is debated. Despite this controversy, the possible influence of supplementary oxygen on animal models of ischaemia-reperfusion injury or cardioprotection is rarely considered. We used an in vivo mouse model of ischaemia and reperfusion to investigate the effect of ventilation with room air versus 100% oxygen. The coronary artery of anaesthetized mice was occluded for 40 min. followed by 2-hrs reperfusion. Infarct size was measured by tetrazolium staining and expressed as a percentage of area at risk, determined using Evan's blue...
October 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28373526/remote-ischaemic-conditioning-in-carotid-artery-stenting-another-step-on-the-journey-toward-clinical-translatability
#19
EDITORIAL
Robert M Bell, Derek M Yellon
No abstract text is available yet for this article.
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28340182/novel-targets-and-future-strategies-for-acute-cardioprotection-position-paper-of-the-european-society-of-cardiology-working-group-on-cellular-biology-of-the-heart
#20
Derek J Hausenloy, David Garcia-Dorado, Hans Erik Bøtker, Sean M Davidson, James Downey, Felix B Engel, Robert Jennings, Sandrine Lecour, Jonathan Leor, Rosalinda Madonna, Michel Ovize, Cinzia Perrino, Fabrice Prunier, Rainer Schulz, Joost P G Sluijter, Linda W Van Laake, Jakob Vinten-Johansen, Derek M Yellon, Kirsti Ytrehus, Gerd Heusch, Péter Ferdinandy
Ischaemic heart disease and the heart failure that often results, remain the leading causes of death and disability in Europe and worldwide. As such, in order to prevent heart failure and improve clinical outcomes in patients presenting with an acute ST-segment elevation myocardial infarction and patients undergoing coronary artery bypass graft surgery, novel therapies are required to protect the heart against the detrimental effects of acute ischaemia/reperfusion injury. During the last three decades, a wide variety of ischaemic conditioning strategies and pharmacological treatments have been tested in the clinic - however, their translation from experimental to clinical studies for improving patient outcomes has been both challenging and disappointing...
March 17, 2017: Cardiovascular Research
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