RESEARCH PORTFOLIO CENTER FOR CIRCULATORY HEALTH

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1 UMC Utrecht Center for Circulatory Health RESEARCH PORTFOLIO CENTER FOR CIRCULATORY HEALTH We shape the future of cardiovascular medicine University Medical Center Utrecht

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3 Table of contents Introduction 3 Research area: Proteomics and Biomarkers 4 Gerard Pasterkamp, Professor of Experimental Cardiology Research area: Genetics 6 Paul de Bakker, Professor of Genetic Epidemiology and Bioinformatics Research area: Molecular and Cellular Biology 8 Marc Vos, Professor of Medical Physiology Research area: Metabolism 10 Eric Kalkhoven, Associate Professor of Metabolic Diseases Research area: Imaging 12 Tim Leiner, Professor of Radiology Research area: Clinical Interventions and Therapeutic Innovations 14 Diederick E. Grobbee, Professor of Clinical Epidemiology Research area: Clinical Research Methods 16 Carl Moons, Professor of Clinical Epidemiology Research area: Prevention and Public Health 18 Jet Smit, Professor of Public Health Research area: Cardiovascular Regenerative Medicine 20 Steven Chamuleau, Associate Professor of Cardiology Colofon 23

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5 Introduction UMC Utrecht Center for Circulatory Health Cardiovascular disease continues to have extensive impact worldwide. Despite the many advances in prevention, intervention, and treatment, diseases affecting the circulatory system maintain a significantly high disease burden. Cardiovascular disease remains as the number one cause of death among women and the second leading cause of death in men. The challenges we face are multifaceted; an aging population, genetic factors, and the rise in cardiovascular risk factors, such as obesity and type II diabetes. To face these challenges the teams within the UMC Utrecht Circulatory Health employ a multidisciplinary, integrated approach to advancing cardiovascular research and care. Integrated Research and Care While many research institutes advocate multidisciplinary and translational research, the true challenge lies within being capable to integrate basic and applied research and care. A successful union is one that can bring results from lab to the patient s bedside whilst simultaneously delivering findings from patient studies back to the lab, creating a continuous cycle of development. By bringing our varied networks and their expertise together, we nurture an environment of collaboration, open discourse and innovation. Center for Circulatory Health Our cardiovascular researchers and clinicians from UMC Utrecht have embarked on an ambitious enterprise with the union of our clinical infrastructure within the Center for Circulatory Health. Our aim is to realize a truly multidisciplinary, integrated approach to research and care. Through this true integration of these ethos, we can adeptly provide treatment to patients while simultaneously conducting relevant clinical research that can deliver results that serve the public immediately. Our ambition is to be the leader in scientific knowledge in the areas of prevention, prediction and prognosis of cardiac disease, stroke and peripheral artery disease, and risk assessing factors such as diabetes and renal failure. Research areas The Center for Circulatory Health portfolio consists of nine research areas. In each area, a different methodological approach is applied to gain knowledge and insight about patients and diseases, resulting in improved prediction, prognosis and prevention. Every research area covers a range of patient groups. The research areas do not operate separately, but collaborate and interact, offering opportunities for cross-fertilization between findings and clinical applications. In this brochure we present our nine multidisciplinary research areas: Proteomics and Biomarkers, Genetics, Molecular and Cellular Biology, Metabolism, Imaging, Clinical Interventions and Therapeutic Innovations, Clinical Research Methods, Prevention and Public Health and Cardiovascular Regenerative Medicine. Center for Circulatory Health 3

6 4 UMC Utrecht We focus on the identification of relevant biomarkers that offer insight into disease development. This information can be used for both prevention, diagnostics and prognostics and therapeutics.

7 Research area: Proteomics and Biomarkers Gerard Pasterkamp, Professor of Experimental Cardiology Until recently, the cardiovascular prognosis of a patient was based on a few traditional risk factors: blood pressure, gender, diabetes, weight, cholesterol levels, age and smoking. Within the field of Proteomics and Biomarkers, we are discovering new parameters that are associated with clinical outcome. Such parameters, named biomarkers, improve cardiovascular risk assessments and will enable us to provide better individualized patient care. The research area Proteomics and Biomarkers focuses on the discovery of molecules derived from the body, in order to predict adverse events and to provide insight into the aetiology of cardiovascular disease processes. The driving force behind all these developments is the creation of large biobanks of different patient populations with different body samples, including serum and plasma, atherosclerotic plaques, adipocytes and circulating cells. A recent methodological revolution in molecular biological techniques that maps the entire spectrum of proteins, lipids, metabolites, or genetic material from a body sample, now enables large scale biomarker discovery. The unique availability of such a wide variety of biobanks in the UMC Utrecht, and our expertise in high throughput molecular biological techniques, enables us to perform innovative biomarker research. By correlating newly discovered biomarkers to real life outcome measures, disease patterns can be derived, and can lead to novel diagnostic and therapeutic applications within the cardiovascular field. Center for Circulatory Health 5

8 6 UMC Utrecht With technological advances made in the past decade, we are in a much better position to understand the genetic basis of cardiovascular disease.

9 Research area: Genetics Paul de Bakker, Professor of Genetic Epidemiology and Bioinformatics Cardiovascular diseases are not simple monogenetic disorders. They are caused by the complex interaction among a large number of genes and environmental factors, including diet and lifestyle. The main interest of the research area Genetics is to identify genetic susceptibility factors for a broad range of cardiovascular diseases, offering insight into the aetiology of these diseases. In addition to finding genetic loci associated with disease, we work to elucidate the underlying biological mechanisms, assessing the potential for individual prevention and prognosis of disease. We specifically focus on arrhythmias, cardiomyopathies, electrocardiographic traits, hypertension, ischemic stroke and aneurysms. Thanks to the Utrecht Cardiovascular Cohort, we can pursue all these questions in targeted patient groups. In addition to having excellent high-throughput sequencing facility, analysis expertise and several well-defined patient cohorts, the strength of the UMC Utrecht cardiovascular genetics research lies in its extensive network with other leading scientists in the Netherlands and abroad, enabling large-scale collaborative studies that are essential for this type of research. Center for Circulatory Health 7

10 The lab plays a central role in every cardiovascular research project. It enables us to not only identify correlations, but also to deliver knowledge to build upon clinical applications. 8 UMC Utrecht

11 Research area: Molecular and Cellular Biology Marc Vos, Professor of Medical Physiology The two questions at the core of the research area Molecular and Cellular Biology are What are the mechanisms of cardiovascular disease and how can we use this knowledge to diagnose and predict disease progression? Research in other areas, such as Imaging, Genetics, Proteomics or Epidemiology, correlates biomarkers or lifestyle factors with disease progression. The molecular and cellular biology lab further investigates these correlations, to unravel the underlying disease mechanisms. Our labs offer cell lines, molecular interventions, (transgenic) animal models, clinical chemistry, and physiological readout equipment. In collaboration with the nearby Hubrecht Institute, high throughput screenings can be performed to identify drug targets. Adjacent to this branch of basic science, we collaborate with industry in order to develop innovative medical applications. A successful example of these collaborations is the Octopus: a device that is attached to the heart during open heart surgery. Making the traditional heart lung machine obsolete, enabling more secure and less intensive surgeries. Center for Circulatory Health 9

12 I would love to acquire an integrated view on the interaction between metabolism and cardiovascular disease, by looking at different metabolic levels. 10 UMC Utrecht

13 Research area: Metabolism Eric Kalkhoven, Associate Professor of Metabolic Diseases The metabolic system plays a central role in the development of cardiovascular disease, as two of the major cardiovascular risk factors have a metabolic origin: obesity and diabetes type II. The Metabolism research area focuses on the signalling between metabolic organs and the cardiovascular system. By understanding the origins of systemic inflammation, it helps us to battle atherosclerosis, atherothrombosis and plaque rupture. Laboratory studies are combined with in vivo approaches and population studies to study metabolic signalling. A strong connection between the lab and clinic is therefore maintained. Our research area is leading when it comes to uncovering adipose tissue function and its role in whole body metabolism. This provides new insights into the aetiology of insulin resistance, which is strongly associated with vascular disease. Finally, high-throughput assays are used to discover hormone-like factors or metabolites that are effectors of disease processes, in particular in cardiovascular disease. Center for Circulatory Health 11

14 Imaging can unveil the cumulative effects of genetic make-up and all other risk factors on the heart and vascular system 12 UMC Utrecht

15 Research area: Imaging Tim Leiner, Professor of Radiology Modern cross-sectional imaging techniques enable visualization and precise quantification of pathologic changes in the vasculature as well resulting end-organ damage due to atherosclerosis and other diseases. The cardiovascular imaging research program is focused on: 1) Development of new cardiovascular imaging techniques; 2) Development of methods to quantify vascular and end-organ damage, and 3) Assessment of the value of imaging for individualized risk assessment. We develop new techniques based on magnetic resonance imaging (MRI), computed tomography (CT) and molecular imaging techniques such as positron emission tomography (PET) and apply them in clinical practice. This research line has a highly translational character. Imaging researchers participate in broad, multidisciplinary collaborations that seek to understand the relation between pathophysiology, genetics, biochemistry, and the resulting structural changes in the vasculature and end organs. To precisely quantify these changes, image-processing scientists develop algorithms to semi-automatically extract this information. Cardiovascular imaging techniques are not only important for diagnosis, but also for prognosis and prevention. Research in this area is carried out together with the epidemiologists and focused on improving prediction of future cardiovascular events in individual patients. Center for Circulatory Health 13

16 14 UMC Utrecht Our strength is our ability to combine the quality and expertise across different disciplines.

17 Research area: Clinical Interventions and Therapeutic Innovations Diederick E. Grobbee, Professor of Clinical Epidemiology The research area Clinical Interventions and Therapeutic Innovations develops and tests the safety and efficacy of novel medical interventions. It is aimed at scientific innovations in the prevention and treatment of cardiovascular disease. and proteomics enable the assessment of individual responses to the benefits and risks of drugs. This research area will be leading in all these developments. The focus is on clinical interventions, but the research area stretches out to cost effectiveness analyses, and the prediction of patient group response based on several genetic and non-genetic factors. This opens up opportunities for personalized prevention, and treatment of cardiovascular diseases. The research translates basic study findings on novel therapeutic agents and biomarkers to the clinical arena. The availability of biomarkers and advanced imaging that are useful to predict disease early in its onset, has opened up the opportunities to study early treatment of individuals at high risk for cardiovascular disease before the clinical symptoms appear. Currently, UMC Utrecht researchers are involved in clinical trials spanning over 30 countries in four continents. The UMC Utrecht has an excellent record in late phase clinical trials, notably in the study of innovative drug treatments, devices and nutritional interventions. It will continue organizing leading clinical trials, using high-quality support facilities for design, biostatistics, data management and coordination. In the field of cardiovascular research, the focus is on transferring results from bench to bedside. Strong pre-clinical research makes first in man studies a realistic goal. Advances in genomics Center for Circulatory Health 15

18 The number and size of cardiovascular studies is rapidly expanding. Innovative methods are necessary to keep the overview 16 UMC Utrecht

19 Research area: Clinical Research Methods Carl Moons, Professor of Clinical Epidemiology At the core of clinical research are issues concerned with how to design, conduct, analyse and report the studies in an ethical, efficient and scientifically sound way. The research area Clinical Research Methods aims to improve the methodology of all clinical epidemiological research: from randomised intervention studies to non-randomised etiologic studies; from research on the discovery and evaluation of diagnostic and prognostic tests and (bio) markers to systematic reviews and metaanalytical research. Approximately sixty percent of the work within this research area consists of methodological research. The remainder consists of methodological and ethical guidance towards other cardiovascular researchers both within and outside of UMC Utrecht. Researchers working in this research area have substantial expertise in the development and application of novel methods for diagnostic and prognostic tests or (bio) marker studies. Their focus lies on the development, validation, and implementation of clinical prediction models or decision protocols. In addition, they develop novel designs and analyses of randomised trials and meta-analyses, to increase the clinical value and significance of such studies. Another research line comprises health technology assessment, intended to rapidly estimate the benefits, risks and monetary costs of health care interventions. Also within this group is a branch of ethics research that delves into the conditions that make responsible innovation in drug development possible. Center for Circulatory Health 17

20 18 UMC Utrecht Disease prevention is not only cost reduction, but health gain above all.

21 Research area: Prevention and Public Health Jet Smit, Professor of Public Health How to improve the health status of the general population is the overarching question in public health. Attractive living conditions which invite to adopt and maintain a healthy life style in a natural way, are paramount in preventing disease and in limiting health care use. This can be achieved by intensive collaboration between science, policy and practice within and beyond the health care domain. The research area Prevention and Public Health brings basic and applied health sciences together to identify and implement effective methods for the prevention of cardiovascular disease. Investigators involved in this research area are developing methods for prevention of cardiovascular disease in the general population and in patient groups with high vascular risks; they are studying early clinical warning signs of developing disease and unraveling mechanisms involved in the development of adverse vascular conditions. The common denominator however is a significant further reduction of cardiovascular diseases in the general population. How can this be achieved? In particular the availability of large cohorts consisting of healthy population samples and patients, covering all age ranges from prenatal life to old age, and containing a wide range of clinical, biological, environmental and lifestyle data, opens up immense potential to collaborate within the research area and to produce the required knowledge to advance cardiovascular disease prevention in the general population and in high-risk patients. High cholesterol and high blood pressure, besides smoking, have a major impact on the population burden of cardiovascular disease. These conditions can be treated by prescription of medication, but rather would we prevent medication use by reducing risk factor prevalence and obtaining a significant improvement of healthy lifestyle in the general population that does not depend solely on the ability to adopt a healthy lifestyle. To do so, we need to develop local, national and global strategies to improve living conditions such that a healthy lifestyle becomes easy, attractive and attainable for every individual in society regardless of age, societal status, ethnicity and gender. The broad range of research disciplines within the research area and the Circulatory Health Program put us in an excellent position to contribute to this goal. Center for Circulatory Health 19

22 20 UMC Utrecht Regenerative Cardiac medicine is a very young discipline with a great deal still to be discovered, but the possibilities are vast

23 Research area: Cardiovascular Regenerative Medicine Steven Chamuleau, Associate Professor of Cardiology One of the great successes in modern cardiovascular medicine comes from the enormous progress in the development of angioplasty and stent placements. While we now see very high survival rates from heart attacks, these very same patients, then face deteriorating cardiac function from scar tissue. This among other concerns drive the research area Regenerative Medicine to boost the repair mechanisms of the heart and other organs within the cardiovascular axis through the use of stem cells and smart biomaterials, with the hope of strengthening the body s ability to heal itself. This drive is fostered through our many multilateral collaborations, such as with the Hubrecht Institute and T/U Eindhoven. Our research is translational in nature, covering the range from basic research to clinical trials. Our studies include many areas from novel treatments for kidney damage using stem cells, to developing smart biomaterials that stimulate the bodies regeneration of defective heart valves, and the use of imaging techniques in chorus with 7T MR, advanced echocardiography and histology/biobanking of bone marrow, skin, artery and veins with the ultimate aim of restoring areas around the border of damaged sites, to name a few. The stakes are high, as are expectations, yet our discipline takes tremendous time, effort, invention, and patience to advance with expected high quality research. While the going can be slow at times, each movement brings us a step closer to the discoveries of new frontiers in medicine. Center for Circulatory Health 21

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25 Colofon For more information, please visit our website Photography and Design Multimedia, UMC Utrecht Printing Zuidam Uithof Drukkerijen Issue Center for Circulatory Health, UMC Utrecht January 2015 Center for Circulatory Health 23

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28 Visting address: Heidelberglaan CX UTRECHT Room STR Correspondence: Postbus GA UTRECHT STR Circulatoryhealth T. +31 (0) Follow us on