Author
Derek M. Yellon
Other affiliations: National University of Singapore, St Thomas' Hospital, University College Hospital ...read more
Bio: Derek M. Yellon is an academic researcher from University College London. The author has contributed to research in topics: Ischemic preconditioning & Cardioprotection. The author has an hindex of 122, co-authored 638 publications receiving 54319 citations. Previous affiliations of Derek M. Yellon include National University of Singapore & St Thomas' Hospital.
Papers published on a yearly basis
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TL;DR: This review focuses on the mechanisms of the injury, on attempts to protect the heart against it, and on promising new approaches to cardioprotection during percutaneous coronary intervention.
Abstract: Lethal reperfusion injury is a paradoxical type of myocardial injury caused by the restoration of coronary blood flow after an ischemic episode. This review focuses on the mechanisms of the injury, on attempts to protect the heart against it, and on promising new approaches to cardioprotection during percutaneous coronary intervention.
3,179 citations
TL;DR: A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.
Abstract: Acute myocardial infarction (MI) is a major cause of death and disability worldwide. In patients with MI, the treatment of choice for reducing acute myocardial ischemic injury and limiting MI size is timely and effective myocardial reperfusion using either thombolytic therapy or primary percutaneous coronary intervention (PPCI). However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is still no effective therapy. A number of new therapeutic strategies currently under investigation for preventing myocardial reperfusion injury have the potential to improve clinical outcomes in patients with acute MI treated with PPCI.
1,666 citations
TL;DR: The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion and are encouraged to adopt in the hope that this will improve uniformity and interlaboratory comparisons.
Abstract: The Lambeth Conventions are guidelines intended to be of practical value in the investigation of arrhythmias induced by ischaemia, infarction, and reperfusion. They cover the design and execution of experiments and the definition, classification, quantification, and analysis of arrhythmias. Investigators are encouraged to adopt the conventions in the hope that this will improve uniformity and interlaboratory comparisons.
1,105 citations
TL;DR: The understanding of the mechanisms associated with preconditioning are unravelled can look forward to the development of new therapeutic agents with novel mechanisms of action that can supplement current treatment options for patients threatened with acute myocardial infarction.
Abstract: Yellon, Derek M., and James M. Downey. Preconditioning the Myocardium: From Cellular Physiology to Clinical Cardiology. Physiol Rev 83: 1113-1151, 2003; 10.1152/physrev.00009.2003.—The phenomenon o...
1,089 citations
TL;DR: Pharmacological manipulation and up-regulation of these pro-survival kinase cascades, which the authors refer to as the Reperfusion Injury Salvage Kinase (RISK) pathway, as an adjunct to reperfusion may therefore protect the myocardium from lethal reperfusions-induced cell death and provide a novel strategy to salvaging viableMyocardium and limiting infarct size.
Abstract: Reperfusion is a pre-requisite to salvaging viable myocardium, following an acute myocardial infarction. Reperfusion of ischaemic myocardium, however, is not without risk, as the act of reperfusion itself can paradoxically result in myocyte death: a phenomenon termed lethal reperfusion-induced injury. Therapeutic strategies that target and attenuate reperfusion-induced cell death may provide novel pharmacological agents, which can be used as an adjunct to current reperfusion therapy, to limit myocardial infarction. Recent evidence has implicated apoptotic cell death during the phase of reperfusion as an important contributor to lethal reperfusion-induced injury. Targeting anti-apoptotic mechanisms of cellular protection at the time of reperfusion may therefore offer a potential approach to attenuating reperfusion-induced cell death. In this regard, ischaemia–reperfusion has been shown to activate the anti-apoptotic pro-survival kinase signalling cascades, phosphatidylinositol-3-OH kinase (PI3K)–Akt and p42/p44 extra-cellular signal-regulated kinases (Erk 1/2), both of which have been implicated in cellular survival. Activating these pro-survival kinase cascades at the time of reperfusion has been demonstrated to confer protection against reperfusion-induced injury. We and others have shown that insulin, insulin-like growth factor-1 (IGF-1), transforming growth factor-β1 (TGF-β1), cardiotrophin-1 (CT-1), urocortin, atorvastatin and bradykinin protect the heart, by activating the PI3K–Akt and/or Erk 1/2 kinase cascades, when given at the commencement of reperfusion, following a lethal ischaemic insult. Pharmacological manipulation and up-regulation of these pro-survival kinase cascades, which we refer to as the Reperfusion Injury Salvage Kinase (RISK) pathway, as an adjunct to reperfusion may therefore protect the myocardium from lethal reperfusion-induced cell death and provide a novel strategy to salvaging viable myocardium and limiting infarct size.
1,044 citations
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TL;DR: The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptoses in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptotic proteins.
Abstract: The process of programmed cell death, or apoptosis, is generally characterized by distinct morphological characteristics and energy-dependent biochemical mechanisms. Apoptosis is considered a vital component of various processes including normal cell turnover, proper development and functioning of the immune system, hormone-dependent atrophy, embryonic development and chemical-induced cell death. Inappropriate apoptosis (either too little or too much) is a factor in many human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer. The ability to modulate the life or death of a cell is recognized for its immense therapeutic potential. Therefore, research continues to focus on the elucidation and analysis of the cell cycle machinery and signaling pathways that control cell cycle arrest and apoptosis. To that end, the field of apoptosis research has been moving forward at an alarmingly rapid rate. Although many of the key apoptotic proteins have been identified, the molecular mechanisms of action or inaction of these proteins remain to be elucidated. The goal of this review is to provide a general overview of current knowledge on the process of apoptosis including morphology, biochemistry, the role of apoptosis in health and disease, detection methods, as well as a discussion of potential alternative forms of apoptosis.
10,744 citations
TL;DR: 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation are published.
Abstract: 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)
6,599 citations
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
TL;DR: Current evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion, which is presented in detail in this review.
Abstract: The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.
5,514 citations