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Texto: Keith Channon — Radcliffe Department of Medicine Cookies on this website We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings. Continue Find out more Skip to main content Site Map Accessibility Cookies Contact us Log in Menu Home About us About us Our Divisions Our Clinical Facilities and MRC Units Working at RDM Athena SWAN News Seminars Locations and contact details Research People Study with us Work with us Current vacancies Novo Nordisk - Oxford Fellowships For Staff Contacts, travel and maps Personnel Finance, Grants and Funding Facilities, IT and Health and Safety Graduate Studies Career Development Athena SWAN Communications and public engagement Search People Keith Channon Contact information Email keith.channon@cardiov.ox.ac.uk Telephone +44 (0)1865 572783 PA Dianne Stafford channon_pa@cardiov.ox.ac.uk Research groups Channon Group: Cardiovascular functional genomics and redox signalling Websites British Heart Foundation Funder DPhil projects available Assigning Functional Mechanisms to a New Coronary Artery Susceptibility Gene Keith Channon FMedSci FRCP Field Marshal Earl Alexander Professor of Cardiovascular Medicine Associate Head of Medical Sciences Division (Clinical Research) Nitric oxide and redox signalling in cardiovascular disease We aim to understand how early changes in the endothelium and vascular wall are related to the initiation and development of vascular diseases, with a particular focus on nitric oxide signalling. Diabetes, high cholesterol, smoking and high blood pressure are all associated with abnormalities in the function of the endothelium, the single-cell lining of blood vessels. Of particular significance are abnormalities in the action of nitric oxide (NO), one of several important molecules produced in the endothelium that help to maintain the health of the blood vessel wall. These abnormalities accelerate the processes that lead to vascular disease, including inflammation, thrombosis and atherosclerotic plaque formation. Production of NO, by nitric oxide synthase enzymes, is highly regulated and depends on the co-factor tetrahydrobiopterin, which is made within endothelial cells. Once NO is produced, it interacts with molecular targets in the cell, but is rapidly inactivated by reactive oxygen species (ROS). Nitric oxide synthases can produce ROS as well as NO, the balance between the two determining the biological actions and pathological importance of these pathways. In previous work, we have used both clinical studies and experimental models to explore the role of endothelial nitric oxide synthase and its regulation by tetrahydrobiopterin in vascular disease, in particular the inflammation associated with atherosclerotic plaque formation. We have developed transgenic models to increase tetrahydrobiopterin levels in the endothelium and other cell types, by overexpression of GTP cyclohydrolase 1 (GTPCH), the rate-limiting enzyme in its synthesis. We have also generated targeted knockouts of GTPCH, to work out how tetrahydrobiopterin is involved in normal function in the cardiovascular system elsewhere. In studies of patients with diabetes and coronary artery disease, we have examined changes in endothelial function, and nitric oxide and tetrahydrobiopterin levels, and how these relate to the clinical features of disease. We have carried out clinical trials of treatments to increase tetrahydrobiopterin levels and improve endothelial function. Key publications Tracking Monocyte Recruitment and Macrophage Accumulation in Atherosclerotic Plaque Progression Using a Novel hCD68GFP/ApoE-/- Reporter Mouse-Brief Report. Journal article McNeill E. et al, (2017), Arterioscler Thromb Vasc Biol, 37, 258 - 263 A key role for tetrahydrobiopterin-dependent endothelial NOS regulation in resistance arteries: studies in endothelial cell tetrahydrobiopterin-deficient mice. Journal article Chuaiphichai S. et al, (2017), Br J Pharmacol, 174, 657 - 671 A novel role for endothelial tetrahydrobiopterin in mitochondrial redox balance. Journal article Bailey J. et al, (2017), Free Radic Biol Med, 104, 214 - 225 Recent publications Hyper-acute cardiovascular magnetic resonance T1 mapping predicts infarct characteristics in patients with ST elevation myocardial infarction. Journal article Alkhalil M. et al, (2020), J Cardiovasc Magn Reson, 22 Pressure-bounded coronary flow reserve to assess the extent of microvascular dysfunction in patients with ST-elevation acute myocardial infarction. Journal article Scarsini R. et al, (2019), EuroIntervention The cardiac sympathetic co-transmitter neuropeptide Y is pro-arrhythmic following ST-elevation myocardial infarction despite beta-blockade. Journal article Kalla M. et al, (2019), Eur Heart J Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres. Journal article Kaura A. et al, (2019), BMJ, 367 A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography. Journal article Oikonomou EK. et al, (2019), Eur Heart J, 40, 3529 - 3543 More publications © 2020 Radcliffe Department of Medicine Freedom of Information Privacy Policy Copyright Statement Accessibility Statement About us Our Divisions Investigative Medicine Division Nuffield Division of Clinical Laboratory Sciences Oxford Centre for Diabetes, Endocrinology and Metabolism Division of Cardiovascular Medicine MRC Weatherall Institute of Molecular Medicine MRC Weatherall Institute of Molecular Medicine Our Clinical Facilities and MRC Units Acute Vascular Imaging Centre Cardiovascular Clinical Research Facility Oxford Centre for Clinical Magnetic Resonance Research Working at RDM Equal career opportunities and flexible working Career development and training Athena SWAN News Seminars Locations and contact details Research Cardiovascular Science Haematology and Pathology Diabetes, Metabolism and Endocrinology Cancer Biology Immunology and Infection Stem Cells and Developmental Biology Geratology Experimental Therapeutics Ashrafian Group: Experimental Therapeutics and Clinical Pharmacology Mahmod group Tyler Group Lunter Group: Functional Genomics & Machine Learning Lunter Group People Moustafa Abdalla Ines Abdesselam Adib Abdullah Amanda Adler Satish Adwani Devika Agarwal Olorunsola Agbaje Doaa Ahmed Jila Ajeian Nadia Akawi Naveed Akbar Nasren Akhtar Ioannis Akoumianakis Merve Aksoz Marta Perez Alcantara Yara Alenazi Jack Allen Maryam Alsharqi Sneha Anand Amanda Anderson Agata Antepowicz Charalambos Antoniades Alex Antonopoulos Mahesh Appari Andrew Apps Janhavi Apte Rina Ariga Andrew Armitage Alyssa Armsby Linda Arnold Ritu Arya James Ashford Neil Ashley Nicole Ashman Houman Ashrafian Kate Attfield Christian Babbs Mohsin Badat Ileana Badi Jade Bailey Subita Balaram Abhirup Banerjee Alison Banham Adrian Banning Liliana Barbieri Mike Barnkob Amy Barrett Carole Bataille Matthew Baxter Asha Bayliss Robert Beagrie Daniel Beard John Bell John Bell Elena Benedetto Amanda Bennett Felicity Bennett Nicolas Bery Timothy Betts Ryan Beveridge Shoumo Bhattacharya William Biggs Malenka Bissell Edward Blair Henry Blest Nicholas Blockley Henry Boardman Andrea Borghetto Alessandra Borlotti Jacqueline Boultwood Yavor Bozhilov Adam Braithwaite Robert Brand Matt Brechin Serena Briant Linford Briant Anne Bridgeman Paul Brodersen James Brown Jill Brown Connor Broyles Marella de Bruijn Alastair Buchan Veronica Buckle Paul Buckley Daniel Bulte Martijn van de Bunt Mario Buono Holger Burchert Emma Burke-Smith Oliver Burns Matthew Burrage Shijie Cai David Cain Sarah Califano Ivan Candido-Ferreira Fang Cao Maria Carena Maria Carena Ricardo Carnicer Davide Carone Joana Carrelha Brigid Carter Barbara Casadei Carla Cascone Vincenzo Cerundolo Kuan Cha Hedia Chagraoui Jem Chalk Keith Channon Lise Chauveau Jane Cheeseman Yi-Ling Chen Jili Chen Qian Cheng Amy Chiu Robin Choudhury Constantinos Christodoulides Zoe Christodoulou Sandy Chu Surawee Chuaiphichai Aldo Ciau-Uitz Thomas Clague Sally-Ann Clark Kevin Clark Lynn Clee Liz Cloke Christopher Cole Ruth Coleman Huw Colin-York Michela Colombo Ismael da Conceicao Catriona Conway Daniel Cooke Kerrie Cope Anna Corby Thomas Cornfield Eduardo Calpena Corpas Yvonne Couch Mark Crabtree Fay Croft Heidi Crook Eloise Cross Nicholas Crump Andres Hueso Cuervo Melinda Czéh Liangti Dai Andrea van Dam Rinita Dam Matt Daniels Lorna Daniels Carol Davey James Davies Graham Davies Simon Davis James Dean Rebecca Dean Atanasiu Stefan Demian Niall Dempster Louise Dennis Timothy Dent Geoffrey Denwood Michael Desborough Veronica Alcolea Devesa Matthew Dickinson Marina Diotallevi Tomasz Dobrzycki Cameron Dockerill Michael Dodd Kathleen Dolan Hamid Dolatshad Robert Friedrich Donat Tao Dong Patricia Douglas Gillian Douglas Damien Downes


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256 www.rdm.ox.ac.uk/people/michael-desborough
257 www.rdm.ox.ac.uk/people/veronica-alcolea-devesa
258 www.rdm.ox.ac.uk/people/matthew-dickinson
259 www.rdm.ox.ac.uk/people/marina-diotallevi
260 www.rdm.ox.ac.uk/people/tomasz-dobrzycki
261 www.rdm.ox.ac.uk/people/cameron-dockerill
262 www.rdm.ox.ac.uk/people/michael-dodd
263 www.rdm.ox.ac.uk/people/kathleen-dolan
264 www.rdm.ox.ac.uk/people/hamid-dolatshad
265 www.rdm.ox.ac.uk/people/robert-friedrich-donat
266 www.rdm.ox.ac.uk/people/tao-dong
267 www.rdm.ox.ac.uk/people/patricia-douglas
268 www.rdm.ox.ac.uk/people/gillian-douglas
269 www.rdm.ox.ac.uk/people/damien-downes



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