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https://www.readbyqxmd.com/read/29858664/neural-mechanisms-in-remote-ischaemic-conditioning-in-the-heart-and-brain-mechanistic-and-translational-aspects
#1
REVIEW
Marina V Basalay, Sean M Davidson, Andrey V Gourine, Derek M Yellon
Remote ischaemic conditioning (RIC) is a promising method of cardioprotection, with numerous clinical studies having demonstrated its ability to reduce myocardial infarct size and improve prognosis. On the other hand, there are several clinical trials, in particular those conducted in the setting of elective cardiac surgery, that have failed to show any benefit of RIC. These contradictory data indicate that there is insufficient understanding of the mechanisms underlying RIC. RIC is now known to signal indiscriminately, protecting not only the heart, but also other organs...
June 1, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29766336/ischaemic-preconditioning-protects-cardiomyocytes-from-anthracycline-induced-toxicity-via-the-pi3k-pathway
#2
Angshuman Maulik, Sean M Davidson, Izabela Piotrowska, Malcolm Walker, Derek M Yellon
PURPOSE: Anthracyclines cause chronic irreversible cardiac failure, but the mechanism remains poorly understood. Emerging data indicate that cardiac damage begins early, suggesting protective modalities delivered in the acute stage may confer prolonged benefit. Ischaemic preconditioning (IPC) activates the pro-survival reperfusion injury salvage kinase (RISK) pathway which involves PI3-kinase and MAPK/ERK1/2. METHODS: We investigated whether simulated IPC (sIPC), in the form of a sublethal exposure to a hypoxic buffer simulating ischaemic conditions followed by reoxygenation, protects primary adult rat cardiomyocytes against anthracycline-induced injury...
May 15, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29666943/the-gtn-patch-a-simple-and-effective-new-approach-to-cardioprotection
#3
Derek M Yellon, Zhenhe He, Rayomand Khambata, Amrita Ahluwalia, Sean M Davidson
There remains a significant un-met need to reduce the extent of myocardial injury caused by ischaemia and reperfusion injury in patients experiencing an ST-elevation MI. Although nitric oxide is central to many cardioprotective strategies currently undergoing investigation, cardioprotection from the delivery of nitrates/nitrites has been inconsistently observed. The route of administration appears to be a critical variable. The glyceryl trinitrate (GTN) patch is commonly used as a simple and practical means of delivering nitric oxide to patients with ischaemic heart disease, but whether acute cardioprotection can be achieved by application of a GTN patch has not been investigated before...
April 17, 2018: Basic Research in Cardiology
https://www.readbyqxmd.com/read/29656359/myocardial-infarct-size-reduction-provided-by-local-and-remote-ischaemic-preconditioning-references-values-from-the-hatter-cardiovascular-institute
#4
Xavier Rossello, Zhenhe He, Derek M Yellon
PURPOSE: To accurately estimate the effect size of both local or classic ischaemic preconditioning (IPC) and remote ischaemic preconditioning (RIPC) using a pooling data set of 91 animals. METHODS: We combined all the available mouse data collected from our Institute over the last 3 years regarding (i) local IPC (4 cycles of 5 min of global ischaemia/reperfusion injury, IRI, followed by 35-min ischaemia and 2-h reperfusion) in the Langendorff-isolated perfused mouse heart model and (ii) RIPC (3 cycles of 5 min of limb occlusion followed by 40-min ischaemia and 2-h reperfusion) in the in vivo mouse model...
April 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29584817/cardioprotection-is-no-the-answer-a-renewed-look-at-nitric-oxide-signalling-in-cardiomyocytes
#5
Sean M Davidson, Derek M Yellon
No abstract text is available yet for this article.
March 23, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29582211/the-caspase-1-inhibitor-vx-765-protects-the-isolated-rat-heart-via-the-risk-pathway
#6
Helison Do Carmo, Sapna Arjun, Orlando Petrucci, Derek M Yellon, Sean M Davidson
PURPOSE: Protecting the heart from ischaemia-reperfusion (IR) injury is a major goal in patients presenting with an acute myocardial infarction. Pyroptosis is a novel form of cell death in which caspase 1 is activated and cleaves interleukin 1β. VX-785 is a highly selective, prodrug caspase 1 inhibitor that is also clinically available. It has been shown to be protective against acute IR in vivo rat model, and therefore might be a promising possibility for future cardioprotective therapy...
April 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29184625/confounding-factors-in-vesicle-uptake-studies-using-fluorescent-lipophilic-membrane-dyes
#7
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
#8
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
#9
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...
February 2018: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29143177/the-risk-pathway-and-beyond
#10
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
#11
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...
April 2018: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/29043508/the-role-of-pi3k%C3%AE-isoform-in-cardioprotection
#12
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/therapeutic-strategies-utilizing-sdf-1%C3%AE-in-ischaemic-cardiomyopathy
#13
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 mobilize 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...
March 1, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29030201/sglt2-inhibitors-hypotheses-on-the-mechanism-of-cardiovascular-protection
#14
Robert M Bell, Derek M Yellon
No abstract text is available yet for this article.
June 2018: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28904083/assessing-the-effects-of-mitofusin-2-deficiency-in-the-adult-heart-using-3d-electron-tomography
#15
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
#16
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
#17
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
#18
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...
January 2018: 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
#19
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
#20
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
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