Rudolf de Boer. Paula Da Costa Martins. Ralph van Oort. Kevin Vernooij. Daniël Pijnappels. Lynda Juffermans. Toon van Veen. Peter van der Meer

Transcription

1 Paula Da Costa Martins Ralph van Oort Lynda Juffermans Kevin Vernooij Daniël Pijnappels Toon van Veen Rudolf de Boer Linda van Laake Kim Van der Heiden Matthijs Boekholdt Peter van der Meer Blanche Schroen Joost Daemen Bas Bekkers Daan Westenbrink Bas Kietselaer Marc Brouwer Paul Knaapen Rudolf de Boer Joris de Groot Jolanda van der Velden Fatih Arslan Daphne Merkus Etienne Cramer Saskia Beeres

2 Fatih Arslan, MD PhD UMCU - Cardiology Cardiac repair mechanisms after injury are complex and divers. Molecular changes in cardiac muscle cells as well as immune responses affecting the heart contribute to cell death, fibrosis and heart failure development. Using mesenchymal stem cell-derived exosomes and Toll-like receptors as therapeutic targets, dr. Fatih Arslan aims at reducing cell death and preventing maladaptive remodeling after cardiac injury. His research is funded by ZonMw, the Dutch Heart foundation and through private-public partnerships. Bas Bekkers, MD PhD MUMC - Cardiology My main field of interest is non-invasive cardiac imaging, especially cardiac magnetic resonance imaging (CMR) and echocardiography. My research involves the clinical use of these imaging techniques, to improve our understanding and early detection of cardiovascular disease that ultimately should lead to a further improvement in individual patient outcome. Saskia Beeres, MD PhD LUMC - Cardiology Chronic heart failure is a major healthcare problem associated with high morbidity and mortality. There is a broad variety of treatment options for heart failure patients consisting of lifestyle changes, pharmacological therapy, cardiac resynchronization therapy, revascularization, surgical left ventricular reconstruction, valve surgery, left ventricular assist devices, heart transplantation and cell therapy. Based on the broad clinical experience in our center, our research group constantly aims to improve both patient selection and the different therapeutic modalities itself. Especially, with the use of multimodality imaging, patient selection for cardiac resynchronization therapy, surgical left ventricular reconstruction and mitral valve surgery is being optimized. Furthermore, clinical research is being performed to evaluate the effectiveness of cardiac cell therapy in patients with heart failure and left ventricular dysfunction.

3 Matthijs Boekholdt, MD PhD AMC Cardiology Atherosclerosis is the underlying disease of the arteries that ultimately leads to clinical events, including myocardial infarction, cerebrovascular events and peripheral artery disease. The pathogenesis of atherosclerosis is incompletely understood. Dr. Boekholdt s research work focuses on the role of biomarkers and cardiovascular imaging in understanding the pathogenesis of atherosclerosis. In addition, more recent work involves biomarkers and cardiovascular imaging in the diagnostic work-up of cardiomyopathies and post-infarct remodeling. Marc Brouwer, MD PhD UMCN Cardiology Troponin release in acute coronary syndromes (ACS) is a prognosticator. Whether this is always indicative of infarction is a matter of debate. In fact, a spectrum of injury seems a plausible concept: varying from reversible injury to the representation of definitive cell death. The TRAMICI-group of Dr. Brouwer studies troponin (troponin I,T,C; complex forms, fragments, protein composition) sampled from the cardiac veins, i.e. close to its origin of release. In a spectrum of patients with a non-st elevation ACS (both CK-MB negative and CK-MB positive) troponin release patterns and differences in protein characteristics will be studied. Insights from this study may aid in the identification of a new biomarker that identifies myocardium at risk in an earlier stage of the ischemic process, which could contribute to strategies to reduce myocardial infarction. Etienne Cramer, MD UMCN Cardiology Hypertrophic cardiomyopathy is a heterogenous disease of which the pathogenesis from start, mutation in a gene that encodes a sarcomere protein, to finish, asymmetrical hypertrophy of the heart with heart failure and sudden cardiac death, is incompletely understood. In the development of disease (from start to finish) ischemia is considered to play an important role. Nonetheless, the role of cardiac biomarker release (i.e. sarcomeric proteins, troponin), especially after physical exercise, has not been extensively studied. By gaining more insight in this field of research and associate biomarker release with genetical aspects of the disease and imaging, the ultimate goal is to improve risk stratification in these patients and to come to an individualized intervention that may ameliorate their clinical course.

4 Rudolf de Boer, MD PhD UMCG Cardiology/Experimental Cardiology The disappointing progress in the treatment of heart failure suggest we currently do not fully comprehend the complex pathophysiology of heart failure. My research focuses on novel and specific drivers of heart failure. Our group has discovered several novel factors implicated in heart failure, using a variety of screens. Several novel have been phenotyped and emerged as biomarkers that indicate specific subforms of the disease. Other factors were shown to be involved in heart failure development and are explored as novel targets for therapy. Paula da Costa Martins, PhD MUMC - Cardiology My research is centered on the role of micrornas in regulating different cellular processes that trigger heart failure. These can be divided in two central research lines: I) Regulation of cardiac cell autophagy by mirnas. Cardiomyocyte dropout is a major cellular event in HF and the relevance of autophagy in the process has only recently started to be appreciated. The salutary opposed to detrimental role of autophagy in the heart has been subject of large controversy and by studying the role of mirnas during the process we try to clarify some of the regulatory mechanisms driving cardiac autophagy and define their role in cardioprotection and cell death and II) (Post)transcriptional regulation of angiogenesis during pathological cardiac remodeling. Insufficient angiogenesis is a characteristic of ischemic heart disease leading to HF. Because the growth of vessels is a complex process involving a number of temporally/ spatially regulated molecular and cellular events, we focus our research on identifying and understanding the role of new regulators such as mirnas. Joost Daemen, MD PhD Erasmus MC Cardiology Joost Daemen has been actively involved in a variety of research projects focussed on the long-term effects of coronary stents and revascularization procedures for coronary heart disease. In addition he acts as principel investigator for multipele research projects investigating the safety and efficicacy of percutaneous renal sympypathetic denervation for patients with hypertension, heart failure and atrial fibrillation.

5 Joris de Groot, MD PhD AMC - Cardiology Currently, Joris de Groot s principle aim is to understand the arrhythmogenic mechanism of AF and to improve patient treatment. He set up a translational research line in 2010 concerning mechanism, modulation and therapy for AF, intertwined with the clinical program for thoracoscopic ablation for AF, started in 2008 which is now one of the largest programs in the world. Attracting a highly competitive personal Dekker grant from the Netherlands Heart Foundation allowed him to install an independent research group, now consisting of 3 PhD students, a nurse practitioner in training and several students. Furthermore, he serves as principal investigator for investigator initiated clinical studies and as local investigator for a number of large, multicenter studies on drugs and device therapy for atrial fibrillation. He is also closely involved in local and international, multicenter studies on novel heart rhythm devices such as the subcutaneous ICD and the first-in-men study with a wireless pacemaker. Lynda Juffermans, PhD VUmc Cardiology Microbubbles are tiny gas bubbles (~2-5 μm), originally developed as contrast agents for echocardiography. Nowadays, microbubbles are subject to research for a wide variety of applications, amongst others local drug/gene delivery, sonothrombolysis and molecular imaging of targeted bubbles. We are currently using targeted microbubbles to assist in stem cell delivery in the infarcted heart. Bas Kietselaer, MD PhD MUMC - Cardiology Cardiac CT angiography enables highly detailed non-invasive visualization of vascular structures such as the aorta and coronary arteries. Arterial plaque morphology and distribution have important impact on patient prognosis. Biomarkers provide a readout of biological processes underlying atherosclerosis. Combining biomarker and cardiac CT information will allow better understanding of biologic processes underlying disease. Ultimately, this should enable personalized risk stratification and treatment of patients.

6 Paul Knaapen, MD PhD VUmc - Cardiology Noninvasive imaging for the diagnosis of coronary artery disease is an important and challenging task. Recent developments have enabled to simultaneously visualize the coronary arteries by CT based angiography and quantitative myocardial perfusion using cardiac PET/CT. The research group of dr. Knaapen investigates the diagnostic accuracy of PET/CT to detect coronary artery disease and aims to optimize cardiac hybrid imaging. Moreover, as an interventional cardiologist, he studies the effects of novel percutaneous coronary revascularization strategies on myocardial perfusion. Linda van Laake, MD PhD UMCU Cardiology Circadian (24 hour-) rhythms profoundly influence cardiovascular pathophysiology. Even heart muscle cells in a culture dish keep their 24-hour rhythm. The research group of Dr. van Laake uses stem cells to investigate how these circadian rhythms in the cardiovascular system develop and how they may be used to improve treatment for cardiovascular disease such as myocardial infarction and heart failure. Daphne Merkus, PhD Erasmus MC - Experimental Cardiology Prolonged changes in flow result in structural and functional adaptations of the vasculature. My research focuses on changes in the coronary and pulmonary vasculature. Changes in the coronary vasculature contribute to the progression of left ventricular dysfunction to heart failure. In pulmonary hypertension, alterations in the pulmonary vasculature eventually result in right ventricular failure and patients with pulmonary hypertension have a limited life expectancy. The mechanisms behind these changes in the vasculature are currently unknown and are investigates in several (large) animal models of coronary and pulmonary vascular disease.

7 Daniël A. Pijnappels, MD PhD LUMC - Cardiology Regular and coordinated electrical activation of the heart contributes to optimal cardiac function. Disturbances could lead to lethal ventricular and comorbidity-causing atrial arrhythmias. The group of Dr. Pijnappels studies the origin and underlying mechanisms of these disorders and aims to use these insights for development of novel therapeutic and preventive strategies based primarily on genetic and cellular engineering, ultimately for human application. Blanche Schroen, PhD MUMC - Experimental Cardiology Blanche Schroen is assistant professor at Maastricht University and has a background in molecular biology. Her passion is the world of noncoding RNA molecules and she investigates their contribution to the development of heart failure, with a particular interest in the role of inflammation. As such, her research focuses on the role of non-coding RNAs in the crosstalk between inflammatory and other cardiac cells. Kim van der Heiden, PhD Erasmus MC Cardiology; Biomedical Engineering Atherosclerosis is a lipid- and inflammation driven disease of the arteries that is found at specific locations in de vessel wall, determined by blood flow-induced forces. These forces also play a role in atherosclerotic plaque destabilization, rendering a plaque vulnerable to rupture. Dr. Van der Heiden investigates the biological pathways that are regulated by blood flow-induced forces and their role in atherosclerotic plaque destabilization.

8 Peter van der Meer, MD PhD UMCG Cardiology Heart failure is a devastating disease with high morbidity and mortality rates. The multifactorial nature of the disease makes it difficult to discern early specific pathways leading to the syndrome. The research group of dr. Van der Meer studies sporadic forms of heart failure with a clear trigger and a defined time pattern to find novel disease mechanisms leading to the discovery of novel therapies. Ralph van Oort, PhD AMC Experimental Cardiology The pathology of heart failure is characterized by poorly contracting and dilated ventricles. This remodeling of the heart is associated with maladaptive structural changes in individual cardiomyocytes. The work of Dr. van Oort aims to reveal the molecular and cellular mechanisms underlying this adverse cardiomyocyte remodeling in the failing heart, which could ultimately give rise to a new therapy for heart failure. Jolanda van der Velden, PhD VUmc Physiology The motor proteins (sarcomeric proteins) of the heart muscle enable proper cardiac pump function. Genetic defects in the sarcomeric proteins cause familial cardiomyopathies and heart failure. The research group of Jolanda van der Velden investigates via which mechanisms the genetic defects cause muscle dysfunction, which may ultimately lead to treatments to prevent and reverse cardiac disease.

9 Toon van Veen, PhD UMCU Medical Physiology Appropriate propagation of the electrical impulse in the heart, which underlies cardiac contraction, depends on a delicate interplay between action potential formation, cell-to-cell propagation and the tissue architecture of the myocardium. Both congenital and acquired disturbance of the molecular mechanisms that facilitate these electrophysiological characteristics may lead to life-threatening cardiac arrhythmias that account for a large number of annual (sudden) deaths. The research group of Dr. Van Veen aims to unravel the mechanisms that lead to an increased propensity for arrhythmias during cardiac disease and focuses on new therapeutic strategies to prohibit this maladaptive remodelling within the heart. Kevin Vernooij, MD PhD MUMC - Cardiology The main research topic of dr.vernooy is the pathophysiology of the heart during asynchronous ventricular electrical activation (ventricular pacing, left bundle branch block) and its reversal by restoring a more synchronous ventricular activation by alternative ventricular pacing sites and optimization of cardiac resynchronization therapy. Daan Westenbrink, MD PhD UMCG Experimental Cardiology Myocardial hypertrophy is the evolutionarily conserved reaction to hemodynamic overload or injury, intended to reduce ventricular wall stress. While initially compensatory, reactive hypertrophy ultimately fails and progresses into to a maladaptive cardiomyopathy with decreased survival. It would be therapeutically beneficial to retain the advantageous features of cardiac hypertrophy that reduce wall stress, while preventing its subsequent decompensation. Although multiple factors may stimulate hypertrophy, the coordination of hypertrophic growth is controlled by a limited number of signal transduction pathways. The research of dr. Westenbrink aims to identify those signal transduction events that are responsible for hypertrophy decompensation, which may ultimately lead to novel therapies.