UK Centre for Cardiovascular and Diabetes Research

The University of Leeds

A MAJOR RUSSELL GROUP UNIVERSITY32000 STUDENTS7000 STAFF

CARDIOVASCULAR RESEARCh LAbS

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TEAChING hOSPITALS SERVING ThREE MILLION PEOPLE

LOCATION OF ThE CLINICAL RESEARCh FACILITY

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STRATEGIC IMPORTANCEfrom the Dean, Professor Paul Stewart FMedSci

The Centre has a critical role to play in advancing understanding of cardiovascular disease and diabetes to improve human life

It is an important team effort between the University of Leeds and Leeds Teaching Hospitals Trust and a major priority for our Joint Partnership Board chaired by the Vice Chancellor and Chief Executive of the Trust.

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ThE DISEASE PRObLEM“Why diabetes? Because despite all the improvements we’ve made in medicine and all the innovations we’ve had in surgery, people with type 2 diabetes are three times more likely to die from a heart attack, and they don’t respond nearly as well to treatment for heart failure.”

BHF Professor Mark Kearney was the lead in the BHF’s 2013 advertising campaign ‘We hate heart disease.’

Professor Mark KearneyBritish Heart Foundation Chair of Cardiovascular and Diabetes Research and Consultant Cardiologist

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£14 MILLION OF NEw RESEARCh GRANTS FROM ExTERNAL FUNDERSGrants in 1 year: June 2012 to May 2013

JOhN GREENwOOD, PROFESSOR, CONSULTANT CARDIOLOGIST,

AND bhF SPECIAL PROJECT GRANT hOLDER

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ThE ExTERNAL FUNDING wE RECEIVE hELPS US MAKE A DIFFERENCE IN OUR FIGhT AGAINST hEART DISEASE

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CARDIOVASCULAR DISEASE AND DIAbETES IS A GLObAL ChALLENGEDiabetes is increasingly common world-wide and adversely affects many aspects of the cardiovascular system.

Predictions from the UK Biobank, a major investment to investigate disease in 500,000 UK citizens, show the numbers of people in this cohort predicted to suffer from a specified condition in 2022. Diabetes is the most common problem; myocardial infarction/coronary heart disease and stroke are the next two.

DR JING LI, LECTURER IN CARDIOVASCULAR RESEARCh

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CLINICAL TRIALS2ND NATIONALLY IN RECRUITMENT TO CARDIOVASCULAR CLINICAL TRIALS

CLINICAL TRIALS RESEARCh UNIT

NEw CLINICAL RESEARCh FACILITY

ALISTAIR hALL, PROFESSOR AND CONSULTANT CARDIOLOGIST, AND LEADER

OF CARDIOVASCULAR CLINICAL TRIALS

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STEPhEN whEATCROFT, SENIOR LECTURER, ERC FELLOw, AND CONSULTANT CARDIOLOGIST

CLINICIAN SCIENTISTSUNDERSTANDING VASCULAR INSULIN RESISTANCE

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ExCELLENCE IN RESEARCh IS SUPPORTED bY CUTTING-EDGE FACILITIESThe centre promotes research of the highest standard and greatest impact on patients.

STACY-PAUL wILShAw, SENIOR TRANSLATIONAL RESEARCh FELLOw

IN CARDIOVASCULAR TISSUE ENGINEERING 11

DAVID bEECh, PROFESSOR, DIRECTOR, AND FELLOw OF ThE ACADEMY OF MEDICAL SCIENCES

A hISTORY OF MAKING DISCOVERIES, INNOVATION AND ChANGING PEOPLE’S LIVES…

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hELEN PhILIPPOU, ASSOCIATE PROFESSOR AND LEAD FOR INNOVATION

AIRE STUDY – TREATMENT OF hEART FAILURE

ENGINEERED hEART VALVE

NOVEL ANTICOAGULANTS

ACE2

REDOx CONTROL ThROUGh ION ChANNELS

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FOCUS ON IMAGINGWe have cutting-edge preclinical and clinical cardiovascular imaging facilities and our researchers have pushed the boundaries of imaging and probe technology from single molecules to cells and whole organisms. Our clinical imaging research has informed international practice guidelines and we lead several large ongoing multi-centre imaging trials. Our work showing the superiority of MRI for diagnosing cardiovascular disease has the potential to transform the lives of patients (Lancet, 2012).

SVEN PLEIN, PROFESSOR, CONSULTANT CARDIOLOGIST, AND bhF SENIOR CLINICAL RESEARCh FELLOw14

…wE ENCOURAGE EFFORTS TO TRANSLATE FINDINGS INTO MORE EFFECTIVE PREVENTION AND TREATMENT OF DISEASE

RIChARD CUbbON, CLINICAL LECTURER, bhF INTERMEDIATE RESEARCh FELLOw AND CARDIOLOGIST 15

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wE STIMULATE ENTERPRISE AND KNOwLEDGE TRANSFER TO MEET ThE CARDIOVASCULAR DISEASE AND DIAbETES ChALLENGE

RObERT ARIENS, PROFESSOR, GROUP LEADER, AND bhF PROGRAMME GRANT hOLDER

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wOMAN OF OUTSTANDING AChIEVEMENTEILEEN INGhAMLeeds is a major medical engineering centre for musculoskeletal and cardiovascular diseases. The group won the 2012 Queen’s Anniversary Prize and founded a spin-out company,Tissue Regenix Group PLC which is focussed upon the commercialisation of Leeds acellular biological scaffold technology. It achieved CE Mark for dCELLR Vascular Patch following successful clinical trials. Bespoke bioprocesses for cardiovascular tissues have been developed which remove the cells, cell remnants and functional DNA. Studies have shown that acellular biological scaffolds derived from both allogeneic and xenogeneic tissues are effective for cardiovascular applications. The group’s focus is on clinical translation of additional acellular allogeneic and xenogeneic biological scaffolds for cardiovascular applications.

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LEADER IN DIAbETES AND ThROMbOSISPETER GRANTPeter is Professor of Medicine, Consultant Diabetologist, and Fellow of the Academy of Medical Sciences. He is also BHF Programme Grant holder and Co-chair of the European Association for the Study of Diabetes task force to update guidelines on diabetes and cardiovascular disease. He has particular interest in mechanisms of thrombosis and translational of this new understanding into therapeutic improvements.

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4-YEAR PhD PROGRAMME IN CARDIOVASCULAR DISEASE AND DIAbETES

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ThE CENTRE hAS A UNIQUE STRUCTURE OF MULTIDISCIPLINARY PROGRAMME AND TEChNOLOGY GROUPSCARDIOVASCULAR AND DIAbETES RESEARCh IS IMPORTANT TO ALL OF ThEM.

SREENIVASAN PONNAMbALAM, READER AND DEPUTY PROGRAMME GROUP LEADER

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PROFESSOR MARK KEARNEY Our laboratory, funded by a British Heart Foundation programme grant, is exploring the mechanistic link between endothelial function and insulin resistance.

DR SREENIVASAN PONNAMbALAM Our research is focused on understanding the mechanisms underlying vascular receptor-ligand interactions leading to control or dysfunction of vascular physiology.

PROFESSOR DAVID bEECh The aim of the lab is to make fundamental discoveries relating to trans-membrane calcium and sodium ion movements in mammalian cells, especially regarding ion channels in cells of human vascular diseases and associated conditions.

DR STEPhEN whEATCROFT My research focuses on the use of genetically altered murine models to investigate the effects of insulin and the IGF-binding proteins on vascular biology.

DR KAREN PORTER My group investigates the cellular and molecular pathways that lead to increased coronary heart disease and poor outcomes after arterial bypass grafting in individuals with type 2 diabetes.

DR RIChARD CUbbON Our research is focussed on understanding how insulin resistance and diabetes impact upon the formation and repair of blood vessels, with the aim of establishing novel regenerative therapies.

DR KAREN bIRCh My research group comprises a team of researchers with an intense focus on investigation of the interplay between female reproductive hormone fluctuation, exercise and cardiovascular health and function.

PROFESSOR ASIPU SIVAPRASADARAO My laboratory is interested in understanding the cellular and molecular basis for how oxidative stress affects the biology of vascular and pancreatic cells.

PROFESSOR STUART EGGINTON My group studies the mechanisms of blood vessel growth, using physiological remodelling to devise targetted therapeutic repair of a pathologically damaged microcirculation, and interactions between the cardiovascular and respiratory systems in exercise and hypothermia.

ENDOThELIAL CELL bIOLOGY AND DIAbETES22

PROFESSOR SVEN PLEINMy research is focused on the development, validation and clinical translation of cardiovascular imaging methods, in particular magnetic resonance imaging. I investigate heart failure and ischaemic heart disease.

PROFESSOR DAVID bUCKLEYI work on quantitative magnetic resonance imaging (MRI) with a focus on tracer kinetic analysis of data acquired using dynamic contrast-enhanced MRI.

PROFESSOR JOhN GREENwOODMy research is focused on the diagnosis and treatment of patients with coronary heart disease. In particular, large multi-centre clinical trials of Cardiovascular Magnetic Resonance (CMR) and Percutaneous Coronary Intervention (PCI).

DR STEVEN SOURbRONMy research is in the use of quantitative and functional magnetic resonance imaging to characterize tissue function or metabolic activity. Clinically these data may be used to improve diagnosis, to plan interventions or therapy, or serve as biomarkers to evaluate the response to therapy.

PROFESSOR MIChELLE PECKhAMWe work on molecular motors, the cytoskeleton and muscle differentiation to understand how myosins contribute to skeletal and heart muscle contraction. We are developing and using super-resolution microscopy.

CARDIOVASCULAR IMAGING

ENDOThELIAL CELL bIOLOGY AND DIAbETES

DR JAMES OLIVERI am an adult congenital cardiologist with a research interest in vascular function of patients with repaired coarctation of the aorta.

PROFESSOR ARUN hOLDENMy group constructs computer models of muscular organs that are based on electrophysiological data from membrane, cell and tissue experiments, with organ geometry from magnetic resonance imaging.

DR AZhAR MAQbOOLMy research focuses on the role of matrix proteins in cardiac remodelling following injury and in heart failure- including their utility as markers for sites of remodelling in vivo using MRI and as plasma biomarkers for cardiac disease.

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DR ANGELA CARTERMy research is focussed on identification and functional analysis of genetic and environmental risk factors for cardiovascular disease and clustering of cardiovascular risk factors in subjects with type 2 diabetes mellitus.

PROFESSOR RObERT ARIENSI have found that the 3D structure of the fibrin clot is different in patients with coronary artery disease. My research is focused on mechanisms that regulate clot structure and how resilient it is, with the aim to develop new diagnostics and therapeutics for thrombosis

DR RAMZI AJJANThe bulk of the current work is focussed on analysing the effects of genetic variations in clotting factors (mainly fibrinogen and factor XIII) on clot structure and function using recombinant techniques.

PROFESSOR PETER GRANTMy research addresses the genetic and environmental determinants of fibrin structure/function in relation to insulin resistance, type 2 diabetes and cardiovascular disease.

DR SIKhA SAhAMy research focuses on cellular remodeling and metabolic profiling in stroke, atherosclerosis, diabetes and related cerebrovascular diseases to investigate novel targets and develop diagnostic tools.

DR hELEN PhILIPPOUMy research is focused on understanding mechanisms of thrombosis by characterising the nature of end-stage coagulation protein-protein interactions, regulatory mechanisms and the influence of post-translational modifications of proteins in determining a blood clots resistance to fibrinolysis.

AThEROThROMbOSIS AND DIAbETES

DR ELEANOR SCOTTI study circadian influences on cardio-metabolic outcomes, including translational work on how 24 hour glucose control relates to adverse outcomes in women with diabetes in pregnancy.

DR KIRTI KAINMy research interest is ethnic differences in atherothrombosis and identification of population-appropriate, economic, non-invasive, primary-prevention screening tools for cardiovascular disease in young-apparently-healthy South-Asians in the community.

DR PAUL bAxTERMy research involves the use of large cardiovascular disease registries and advanced biostatistical methods to understand the drivers of patient outcomes and disease mechanisms.

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CARDIOVASCULAR ChEMISTRY TEChNOLOGY GROUP

PROFESSOR COLIN FIShwICKOur research is focused on the application of computer-aided molecular design methods to the production of potent and selective small-molecule inhibitors of a range of therapeutically important enzymes and receptors.

DR RObIN bONWe focus on the development of chemical tools to profile, image and perturb proteins that play a role in cardiovascular disease, which could lead to better mechanistic understanding of the onset/progression of disease and to new lead compounds in the development of diagnostics and drugs.

DR RIChARD FOSTERMy group is interested in the design, synthesis and optimisation of small molecules for therapeutic application or their use in the elucidation of biological function.

IN PURSUIT OF NEw SMALL-MOLECULE MODULATORS, PRObES AND ThERAPEUTICS

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CARDIOVASCULAR ENGINEERING

PROFESSOR EILEEN INGhAMResearch is focused on clinical and commercial translation of acellular allogeneic and xenogeneic cardiac valves and understanding of the mechanisms of acellular biological scaffold regeneration.

DR STACY-PAUL wILShAwResearch is concerned with the development and translation of acellular allogeneic and xenogeneic vascular grafts for repair and replacement of large, medium and small diameter arteries.

PROFESSOR JOhN FIShER FMedSci CBEResearch into acellular biological scaffolds for cardiovascular applications is focused on the development of innovative, robust preclinical bioengineering test methods to ensure safety and reliability.

QUEEN’S ANNIVERSARY PRIZE

wELMEC CENTRE OF ExCELLENCE

TISSUE REGENIx

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hEART FAILURE AND AUTONOMIC CONTROL

DR SARAh CALAGhANMy research focuses on the mechanisms which control the behaviour of individual cardiac muscle cells in the heart in response to a variety of stimuli. This information can be used to understand the function of the heart in both health and disease.

PROFESSOR ALISTAIR hALLI lead a regional network that works to discover, develop and deploy effective strategies to: Identify and understand the mechanism of coronary artery disease. Prevent premature coronary artery disease.

PROFESSOR JOhN TRINICKWe study structure and mechanism in muscle sarcomeres and their isolated component proteins. This includes dilated and hypertrophic cardiomyopathies caused by sarcomere mutations. We specialise in electron microscopy.

PROFESSOR DEREK STEELEMost of my work addresses the sarcoplasmic reticulum Ca2+ channel (ryanodine receptor) in cardiac and skeletal muscle.

DR MARK DRINKhILLMy research focuses on the autonomic control of cardiovascular system and how disease processes such as heart failure can adversely influence this.

PROFESSOR ChRIS PEERSStudies are focused on how physiological gases (oxygen, carbon monoxide and hydrogen sulphide) directly regulate ion channel function and hence various aspects of disease associated vascular smooth muscle and cardiac myocyte activity.

PROFESSOR ED whITEWe investigate the electrophysiological and contractile changes that occur in cardiac muscle in response to physiological (exercise) and pathological (heart failure) stimuli.

PROFESSOR JIM DEUChARSWe investigate the organisation and function of the parts of the brain and spinal cord that contribute to control of the autonomic nervous system.

DR TREVOR bATTENThe aim of my research is to understand the central nervous connections that control the heart, particularly in terms of neurotransmitter-receptor interactions.

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DR KLAUS wITTEMy work focuses broadly on the field of heart failure. My interests include the development of pathways to improve patient access to clinical services, and strategies to promote optimal use of existing drug and device treatments, as well as investigating new treatments.

DR SIMON hARRISONMy research interests lie in understanding the mechanisms of normal excitation-contraction coupling in the heart, how these processes are regulated and how a variety of ‘disease states’ (hypertrophy, sepsis, etc) affect the strength of contraction of the heart.

ChRIS PEERS, PROFESSOR AND GROUP LEADER

hEART FAILURE AND AUTONOMIC CONTROL

DR NEIL TURNERThe general aim of my research is to understand key intracellular signalling mechanisms that regulate adverse remodelling of the cardiovascular system, with particular focus on cardiac fibroblasts.

DR IAN wOODMy group is interested in understanding the mechanisms responsible for altered regulation of gene expression in cardiovascular disease.

PROFESSOR JOhN COLYERMy group is interested in the control of cardiac function via post-translational modification (PTM) of proteins. We use quantitative approaches to explore these events in health and disease.

DR MATThEw LANCASTERWe investigate the progressive changes in the pacemaker and ventricles of the heart with advancing age, which then predispose to problems in old age.

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Professor Martin bennettVessel wall and stem cell-derived cells

Professor Keith ChannonEndothelial redox signalling

Professor Costanza EmanuelimiR targeting for vascular regeneration

Professor David NewbyNovel approaches to cardiovascular imaging

Professor Sussan NoursharghNeutrophil-venular wall interactions in tissue damage

Professor herbert waldmannTarget identification for natural product-inspired compounds

Professor Antonio Vidal-PuigAdipose tissue and the metabolic syndrome

Professor Stefan NeubauerClinical Magnetic Resonance Research

Professor Peter KohlCardiac mechano-electrical interaction

DISTINGUIShED VISITING LECTURER PROGRAMME

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CARDIOVASCULAR DISEASE AND DIAbETES RESEARCh RETREATSTeam building, presentations, and discussions about new ideas, techniques and strategies Ullswater, UK

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Prasai, M.J., Mughal, R.S., Wheatcroft, S.B., Kearney, M.T., Grant, P.J., Scott, E.M. (2013). Diurnal variation in vascular and metabolic function in diet-induced obesity: divergence of insulin resistance and loss of clock rhythm. Diabetes. 62, 1981-1989.

Pieters, M., Kotze, R.C., Jerling, J.C., Kruger, A., Ariëns, R.A.S. (2013). Evidence that fibrinogen gamma’ regulates plasma clot structure and lysis, and relationship to cardiovascular risk factors in black Africans. Blood 121, 3254-60.

Ajjan RA, Gamlen T, Standeven KF, Mughal S, Hess K, Smith KA, Dunn EJ, Anwar MM, Rabbani N, Thornalley PJ, Philippou H, Grant PJ. (2013). Diabetes is associated with post-translational modifications in plasminogen resulting in reduced plasmin generation and enzyme specific activity’. Blood 122, 134-42.

Sukumar, P., Viswambharan, H., Imrie, H., Cubbon, R.M., Yuldasheva, N., Gage, M., Galloway, S., Skromna, A., Kandavelu, P., Santos, C.X., Gatenby, V.K., Smith, J., Beech, D.J., Wheatcroft, S.B., Channon, K.M., Shah, A.M., Kearney, M.T. (2013). Nox2 NADPH Oxidase Has a Critical Role in Insulin Resistance-Related Endothelial Cell Dysfunction. Diabetes 62, 2130-4.

Choe, C.U., Atzler, D., Wild, P.S., Carter, A.M., Böger, R.H., Ojeda, F., Simova, O., Stockebrand, M., Lackner, K., Nabuurs, C., Marescau, B., Streichert, T., Müller, C., Lüneburg, N.,

De Deyn, P.P., Benndorf, R.A., Baldus, S., Gerloff, C., Blankenberg, S., Heerschap, A., Grant, P.J., Magnus, T., Zeller, T., Isbrandt, D., Schwedhelm, E. (2013). Homoarginine levels are regulated by L-arginine:glycine amidinotransferase and affect stroke outcome: results from human and murine studies. Circulation 128, 1451-1461.

Smith, K.A., Pease, R.J., Avery, C.A., Brown, J.M., Adamson, P.J., Cooke, E.J., Neergaard-Petersen, S., Cordell, P.A., Ariëns, R.A., Fishwick, C.W., Philippou, H., Grant, P.J. (2013). The activation peptide cleft exposed by thrombin cleavage of FXIII-A2 contains a recognition site for the fibrinogen α chain. Blood. 121, 2117-26.

Greenwood, J.P., Maredia, N., Younger, J.F., Brown, J.M., Nixon, J., Everett, C.C., Bijsterveld, P., Ridgway, J.P., Radjenovic, A., Dickinson, C.J., Ball, S.G., Plein, S. (2012). Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial. Lancet 379, 453-460.

Dallas, M.L., Yang, Z., Boyle, J.P., Boycott, H.E., Scragg, J.L., Milligan, C.J., Elies, J., Duke, A., Thireau, J., Reboul, C., Richard, S., Bernus, O., Steele, D.S., Peers, C. (2012). Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na Current. Am J Respir Crit Care Med, 186(7), 648-56.

Sukumar, P., Sedo, A., Li, J., Wilson, L.A., O’Regan, D., Lippiat, J.D., Porter, K.E., Kearney, M.T., Ainscough, J.F.X., Beech, D.J. (2012). Constitutively-active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin. Circulation Research 111, 191-200.

Camenzind, E., Wijns, W., Mauri, L., Kurowski, V., Parikh, K., Gao, R., Bode, C., Greenwood, J.P., Boersma, E., Vranckx, P., McFadden, E., Serruys, P.W., O’Neil, W.W., Jorissen, B., Van Leeuwen, F., Steg, P.G., et al. (2012). Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet 380, 1396-405.

Fairbairn, T.A., Meads, D.M., Mather, A.N., Motwani, M., Pavitt, S., Plein, S., Blackman, D.J., Greenwood, J.P. (2012) Serial change in health related quality of life over one year following Transcatheter Aortic Valve Implantation: Predictors of health outcomes. J Am Coll Cardiol 59, 1672-1680.

Myerson S.G., D’arcy, J., Karamitsos, T.D., Francis, J.M., Banning, A.P., Neubauer, S., Mohiaddin, R., Christiansen, J.P., Greenwood, J.P. (2012). Aortic regurgitation quantification using cardiovascular magnetic resonance: Association with clinical outcome. Circulation 126, 1452-1460

McKeown, L., Moss, N.K., Turner, P., Li, J., Heath, N., Burke, D., O’Regan, D., Gilthorpe, M.S., Porter, K.E., Beech, D.J. (2012). PDGF maintains stored calcium through a non-clustering Orai1 mechanism but evokes clustering if the ER is stressed by store-depletion. Circulation Research 111, 66-76.

Imrie, H., Abbas, A., Viswambharan, H., Sukumar, P., Cubbon, R.M., Gage, M., Smith, J., Galloway, S., Yuldeshava, N.Y., Skromna, A., Kahn, M., Futers, S., Aziz, A., Gatenby, V.K., Grant, P.J., Channon, K.M., Beech, D.J., Wheatcroft, S.B., Kearney, M.T. (2012) Novel Role of the IGF-1 receptor in endothelial cell function and repair: studies in endothelium-targeted IGF-1R transgenic mice. Diabetes 61 (9), 2359-68.

Odell, A.F., Hollstein, M., Ponnambalam, S., Walker, J.H. (2012) The VE-cadherin-PAR3-alpha-catenin complex regulates the Golgi localization and activity of cytosolic phospholipase A2alpha in confluent endothelial cells. Mol Biol Cell 23,1783-1796.

wORLD CLASS RESEARCh OUTPUTSwe/The Centre provide an open and flexible organization and a culture of collaboration through which research can be successful

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Rajwani, A., Ezzat, V., Smith, J., Yuldasheva, N.Y., Duncan, E.R., Gage, M., Cubbon, R.M., Kahn, M.B., Imrie, H., Abbas, A., Viswambharan, H., Aziz, A., Sukumar, P., Vidal-Puig, A., Sethi, J.K., Xuan, S., Shah, A.M., Grant, P.J., Porter, K.E., Kearney, M.T., Wheatcroft, S.B. (2012). Increasing circulating IGFBP1 levels improves insulin-sensitivity, promotes nitric oxide production, lowers blood pressure and protects against atherosclerosis. Diabetes 61, 915-924.

Lockie, T.P.E., Perera, D., De Silva, K., Williams, R., Asrress, K.N., Patel, K., Redwood, S.R., Marber, M.S., Rolandi, M.C., Siebes, M., Guilcher, A., Chowienczyk, P., Plein, S. (2012). Synergistic adaptations to exercise in the systemic and coronary circulations that underlie the warm-Up angina phenomenon. Circulation. 126, 2565-2574.

Camenzind E., Wijns W., Mauri L., Kurowski V., Parikh K., Gao R., Bode C., Greenwood J.P., Boersma E., Vranckx P., McFadden E., Serruys P.W., O’Neil W.W., Jorissen B., Van Leeuwen F., Steg P.G., PROTECT Steering Committee and Investigators. (2012) Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial. Lancet. 20, 1396-405.

Jogiya, R., Kozerke, S., Morton, G., De Silva, K., Redwood, S., Perera, D., Nagel, E., Plein, S. (2012). Validation of dynamic 3-dimensional whole heart magnetic resonance myocardial perfusion imaging against fractional flow reserve for the detection of significant coronary artery disease. J Am Coll Cardiol. 60, 756-765.

Lockie, T., Ishida, M., Perera, D., Chiribiri, A., De Silva, K., Kozerke, S., Marber, M., Nagel, E., Redwood, S., Plein S. (2011) High resolution magnetic resonance myocardial perfusion imaging at 3 Tesla to detect haemodynamically significant coronary stenoses as determined by fractional flow reserve. J Am Coll Cardiol 57, 70-75.

Scott, D.J., Prasad, P., Philippou, H., Rashid, S.T., Sohrabi, S., Whalley, D., Kordowicz, A., Tang, Q., West, R., Johnson, A., Woods, J., Ajjan, R.A., Ariëns, R.A. (2011). Clot Architecture Is Altered in Abdominal Aortic Aneurysms and Correlates With Aneurysm Size. Arterioscler Thromb Vasc Biol. 31, 3004-3010.

Cubbon, R.M., Gale, C.P., Kearney, L.C., Schechter, C.B., Brooksby, W.P., Nolan, J., Fox, K.A., Rajwani, A., Baig, W., Groves, D., Barlow, P., Fisher, A.C., Batin, P.D., Kahn, M.B., Zaman, A.G., Shah, A.M., Byrne, J.A., Lindsay, S.J., Sapsford, R.J., Wheatcroft, S.B., Witte, K.K., Kearney, M.T. (2011). Changing characteristics and mode of death associated with chronic heart failure caused by left ventricular systolic dysfunction: a study across therapeutic eras. Circ Heart Fail. 4, 396-403

Agarwal, S.R., MacDougall, D.A., Tyser, R., Pugh, S.D., Calaghan, S.C., Harvey, R.D. (2011). Effects of cholesterol depletion on compartmentalized cAMP responses in adult cardiac myocytes. J Mol Cell Cardiol. 50, 500-509.

Smith, K.A., Adamson, P.J., Pease, R.J., Brown, J.M., Balmforth, A.J., Cordell, P.A., Ariëns, R.A., Philippou, H., Grant, P.J. (2011). Interactions between factor XIII and the alphaC region of fibrinogen. Blood 117, 3460-3468.

Kahn, M.B., Yuldasheva, N.Y., Cubbon, R.M., Surr, J., Rashid, S.T., Viswambharan, H., Imrie, H., Abbas, A., Rajwani, A., Aziz, A., Baliga, V., Sukumar, P., Gage, M., Kearney, M.T., Wheatcroft, S.B. (2011). Insulin resistance impairs circulating angiogenic progenitor cell function and delays endothelial regeneration. Diabetes 60, 1295-303.

Cheong, A, Li, J., Sukumar, P., Kumar, B., Zeng, F., Riches, K., Munsch, C., Wood, I.C., Porter, K.E., Beech, D.J. (2011). Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by Kv1.3 channel blockers. Cardiovasc Res. 89, 282-289.

Naylor, J., Al-Shawaf, E., McKeown, L., Manna, P.T., Porter, K.E., O’Regan, D., Muraki, K., Beech, D.J. (2011). TRPC5 channel sensitivities to antioxidants and hydroxylated stilbenes. J. Biol Chem. 286, 5078-5086.

Konings, J., Govers-Riemslag, J.W., Philippou, H., Mutch, N.J., Borissoff, J.I., Allan, P., Mohan, S., Tans, G., Ten, Cate H., Ariëns, R.A. (2011). Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin. Blood. 118, 3942-3951. 276-85.

Viswanathan, K., Kilcullen, N., Morrell, C., Thistlethwaite, S.J., Sivananthan, M.U., Hassan, T.B., Barth, J.H., Hall, A.S. (2010). Heart-type fatty acid-binding protein predicts long-term mortality and re-infarction in consecutive patients with suspected acute coronary syndrome who are troponin-negative. J Am Coll Cardiol. 55, 2590-2598.

Oke, O.A., Burgess, S.A., Forgacs, E., Knight, P.J., Sakamoto, T., Sellers, J.R., White, H., Trinick, J. (2010). Influence of lever structure on myosin 5a walking. Proc Natl Acad Sci U S A. 107, 2509-2514.

Mutch, N.J., Engel, R., Uitte de Willige, S., Philippou, H., Ariëns, R.A. (2010). Polyphosphate modifies the fibrin network and down-regulates fibrinolysis by attenuating binding of tPA and plasminogen to fibrin. Blood 115, 3980-3988.

AL-Shawaf, E., Naylor, J., Taylor, H., Riches, K., Milligan, C.J., O’Regan, D., Porter, K.E., Li, J., Beech, D.J. (2010). Stimulation of calcium-permeable TRPC5-containing channels by oxidized phospholipids. Arterioscler Thromb Vasc Biol. 30, 1453-1459.

Cordell, P.A., Kile, B,T,, Standeven, K.F., Josefsson, E.C., Pease, R.J., Grant, P.J. (2010). Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion. Blood 115, 2674-2681.

Naylor, J., Li, J., Milligan, C.J., Zeng, F., Sukumar, P., Hou, B., Sedo, A., Yuldasheva, N., Majeed, Y., Beri, D., Jiang, S., Seymour, V.A.L., McKeown, L., Kumar, B., Harteneck, C., O’Regan, D., Wheatcroft, S.B., Kearney, M.T., Jones, C., Porter, K.E., Beech, D.J. (2010). Pregnenolone sulphate- and cholesterol-regulated TRPM3 channels coupled to vascular smooth muscle secretion and contraction. Circulation Research 106, 1507-1515.

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CARDIOVASCULAR AND DIAbETES RESEARCh AT LEEDSwe would be delighted to hear from you with any requests for further information.

DirectorDavid J Beech, FMedSci Professor of Cardiovascular Science

Clinical DirectorJohn P Greenwood MB ChB, PhD, MRCP Professor of Cardiology and Consultant Cardiologist

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The Centre is a partnership between the University of Leeds and the Leeds Teaching Hospitals NHS Trust

Established 2008

FROM DISCOVERY TO PATIENT bENEFITSwww.cardiovascular.leeds.ac.uk

University of LeedsLeeds, United Kingdom

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