Research team

INFLA-MED - Fundamental research in the pathophysiological processes of inflammatory diseases. 01/01/2015 - 31/12/2019

Abstract

The Infla-Med consortium performs fundamental research on the pathophysiological processes of inflammatory diseases (cardiovascular, gastrointestinal, renal and infectious disease) by using a multidisciplinary approach (pathophysiology, pharmacology, biochemistry and medicinal chemistry). The consortium is embedded within the research priorities 'Drug Research' and 'Infectious Diseases' of the University of Antwerp. Recently, the University of Antwerp assigned the Infla-Med consortium as Research Consortium of Excellence.

Researcher(s)

Research team(s)

Endothelial dysfunction in chronic heart failure: a study paradigm to explore novel biomarkers and therapeutic avenues. 01/10/2014 - 24/08/2020

Abstract

The present project has three main aims. The first is to determine the role of endothelial dysfunction in exercise intolerance of CHF patients and to study the effect exercise training. Secondly, we will further explore the potential role of microRNAs in endothelial dysfunction. These microRNAs are short circulating molecules that regulate gene expression. We will investigate if such microRNAs might be useful as biomarkers for exercise capacity in CHF patients. The third aim is to investigate and possibly modify crucial pathways that are responsible for the bone marrow dysfunction that is found in CHF patients. This bone marrow malfunction also affects the bone marrow derived progenitor cells that are crucial in the process of endothelial repair.

Researcher(s)

Research team(s)

    High-Frequency Ultrasound Imaging System Vevo 2100. 19/05/2014 - 31/12/2018

    Abstract

    This project represents a formal research agreement between UA and on the other hand the Hercules Foundation. UA provides the Hercules Foundation research results mentioned in the title of the project under the conditions as stipulated in this contract.

    Researcher(s)

    Research team(s)

    Role of dendritic cells in Th1/Th17-mediated immune diseases. 01/01/2013 - 31/12/2016

    Abstract

    Dendritic cells (DCs) are central mediators that keep the balance between immunity to foreign antigens and immune tolerance to self-proteins. Disruption of this balance may lead to disease. We aim to unravel the role of DCs in T-helper (Th)1/Th17-mediated immune diseases (including inflammatory bowel disease, multiple sclerosis, cardiovascular disease and rheumatoid arthritis), with the purpose to design novel DC-targeted therapeutic strategies.

    Researcher(s)

    Research team(s)

      Bone marrow dysfunction and reversibility in patients with ischemic cardiomyopathy. 01/01/2013 - 31/12/2013

      Abstract

      This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

      Researcher(s)

      Research team(s)

        Adiponectin: Potential therapeutic target for the treatment of muscle wasting in chronic heart failure. 01/01/2013 - 31/12/2013

        Abstract

        During the past decade, cachexia in the setting of severe CHF has gained considerable attention. Loss of skeletal muscle mass as well as structural and functional changes, however, occur already early in the disease process. Interestingly, even after correction for reduced muscle mass, it appears that muscle quality is also affected. This has led investigators to launch the concept of "heart failure myopathy". Energetic deprivation has been attributed a key role in the pathophysiological cascade of events. Amongst a whole series of recently discovered adipokines, adiponectin may well play a fundamental role in the energy – deprived status in CHF. Recent data provided evidence of a functional adiponectin resistance at the level of the skeletal muscle in CHF patients. The aim of this study is to explore the role of adiponectin in CHF, in particular the underlying mechanisms of adiponectin resistance and this, for the first time, in an in vitro setting.

        Researcher(s)

        Research team(s)

          Pathophysiological determinants of exercise intolerance in chronic heart failure; focus on endothelial and skeletal muscle dysfunction. 01/10/2012 - 12/12/2013

          Abstract

          The present projects aim to i) investigate and modify pathways, responsible for deficient bone marrow (BM)-related progenitor cells, which are considered key players in the process of endothelial repair; ii) study the effect of ventricular assist support on ED and repair, as well as exercise capacity, in patients with terminal heart failure and to relate these findings to BM suppression (see i); iii) further explore the contribution of skeletal muscle-derived adiponectin to the circulating pool and to clarify the relevance of the recently demonstrated concept of adiponectin resistance, in mediating skeletal muscle wasting; iv) test and explain the effects of exercise training, through modulation of i-iii.

          Researcher(s)

          Research team(s)

            Next generation sequencing technology opening new frontiers in biological and medical research. 28/06/2012 - 31/12/2017

            Abstract

            The aim of this project is to develop a next generation sequencing (NGS) platform to advance in a collaborative way biological and medical research within the Antwerp research community. The consortium involves more than 16 research groups in various disciplines of medicine, biology and biomedical informatics. The goals are to identify new genes and mutations in various rare Mendelian disorders, to achieve more insights in the genetic causes of cancer and to unravel more precisely the genetic determinants of infectious diseases. This new knowledge will improve both the diagnosis and management of these human diseases. The project will also focus on the interaction between environment and genes. More specifically, the effect of environmental stressors on genetic variation in aquatic organisms, the effect of teratogenic factors on embryonic development in vertebrates and the effects of environmental conditions on growth in maize and Arabidopsis lines will be studied. The analysis of the large amount of genomic and transcriptomic data, generated by the various research groups, will be coordinated by the recently founded UZA/UA bioinformatics group Biomina

            Researcher(s)

            Research team(s)

            The extent of bone marrow dysfunction and the potential to reverse underlying mechanisms in patients with ischemic cardiomyopathy. 01/01/2012 - 31/12/2015

            Abstract

            The proposed project approach will create unique opportunities to describe the extent of bone marrow dysfunction in patients with ischemic heart disease and to explore underlying mechanisms. As such, it might be possible to identify reversible pathways that should be targeted in order to functionally rejuvenate "sick" autologous bone marrow-derived stem cells. The combination of gene and cell therapy has the potential to create tailored therapy, ultimately improving morbidity and mortality of patients with cardiovascular disease.

            Researcher(s)

            Research team(s)

              Clinical and (patho)genetic study of bicuspid aortic valve and associated aortic aneurysm. 01/01/2012 - 31/12/2015

              Abstract

              The general aim of this project is to gain insight into the clinical course of BAV-associated TAA, into the pathogenic mechanisms leading to aneurysm formation and to unravel the underlying genetic basis. In this project we will correlate a specific subclassification of bicuspid aortic valves (Sievers classification) with cardiovascular characteristics including co-morbidity, arterial stiffness and eccentric flow patterns. In addition, we will investigate the contribution of different developmental pathways and identify the genetic basis using state-of-the-art techniques including microRNA profiling, Copy Number Variant analysis and exome sequencing.

              Researcher(s)

              Research team(s)

              The role of autophagy in lethal reperfusion injury following myocardial infarction and the effect of postconditioning in relation to adiponectin plasma levels. 01/01/2011 - 31/12/2014

              Abstract

              In this study, we will investigate the role of autophagy (a cell survival and death pathway) and adiponectin (an endogenous hormone produced by fat cells) in a protective post-myocardial infarction reperfusion therapy called postconditioning. Adiponectin has protective myocardial effects that limit lethal reperfusion injury. However, patients with central obesity have low plasma levels of adiponectin, which may confound the cardioprotective properties of postconditioning.

              Researcher(s)

              Research team(s)

                Peripheral skeletal muscle disorders in patients with chronic heart failure: study of the basic mechanisms and impact of physical training. 01/10/2010 - 30/09/2011

                Abstract

                In the next 2 years, we first plan to investigate the effect of exercise training on metabolic gene expression at the level of the skeletal muscle. Next, we would like to explore the underlying mechanisms and possible hypothesis for the observed abnormalities using myoblastcultures. Further, the hypothesis of adiponectin as a biomarker for wasting in CHF will be explored by correlating adiponectin levels with measurements of muscle strength and muscle mass (CT scan). Finally, we will compare the observed metabolic disturbances in our CHF patients with another population characterized by insulin resistance, metabolic syndrome patients.

                Researcher(s)

                Research team(s)

                  Chronic kidney disease and cardiovascular risk: endothelial dysfunction at the interface? 01/10/2010 - 30/09/2011

                  Abstract

                  In the present project, we focus on endothelial dysfunction in CKD patients. Endothelial dysfunction precedes overt atherosclerotic changes of the vascular wall by many years. Interestingly, in the absence of structural changes, endothelial dysfunction is still reversible, which offers therapeutic perspectives to tackle the progression towards atherosclerosis in an early stage. Several mechanisms for the development of endothelial dysfunction will be investigated, with special emphasize on mechanisms that repair the vascular wall. Moreover, we will study the possible beneficial effect of physical exercise on endothelial function in CKD patients.

                  Researcher(s)

                  Research team(s)

                  Adolescent obesity; what determines endothelial dysfunction and is the process reversible? 01/07/2010 - 30/06/2014

                  Abstract

                  Endothelial dysfunction is already manifest in obese children. Physical activity and diet are efficient measures to tackle obesity. 2 cohorts of obese adolescents are recruted dietary advise and encouragement of sports vs supervised diet and training (10 mths). Improved endothelial-dependent vasodilation serves as a primary endpoint. Metabolic/inflammatory changes, oxidative stress, mobilisation/function of endothelial progenitor cells (endothelial repair) is examined. Endothelial damage is assessed through liberation of endothelial microparticles.

                  Researcher(s)

                  Research team(s)

                    Expression of vascular adhesion molecules on endothelial progenitor cells and their relation to the homing capacity of these cells towards sites of tissue ischemia. 01/10/2009 - 30/09/2011

                    Abstract

                    This project proposal aims at verifying in which way the different homing signals originating from ischemic tissue lead endothelial progenitor cells - via induction of the PI3K-Akt-eNOS pathway - to express cellular adhesion molecules, which results in efficient homing, adhesion and diapedesis.

                    Researcher(s)

                    Research team(s)

                      Effect of exercise on mobilisation and function of endothelial progenitor cells in chronic heart failure. 01/10/2008 - 30/09/2010

                      Abstract

                      In this study, the effect of exercise on the number and function of circulating endothelial progenitor cells (EPC), is evaluated in chronic heart failure patients. A single bout of maximal exercise as well as a physical training program are investigated as stimuli for the release of EPC. Underlying physiological mechanisms are assessed and special attention goes to homing factors, nitric oxide and oxidative stress. Healthy subjects and patients with coronary artery disease will serve as a control group.

                      Researcher(s)

                      Research team(s)

                        Role of eNOS uncoupling in heart failure. 12/03/2008 - 31/12/2009

                        Abstract

                        The last years, eNOS-uncoupling became an important new concept in the cardiopathogenesis of myocardial infarction and endothelial dysfunction. Recently, dr. Moens published in two independent Circulation papers the possibility to prevent and reverse eNOS-uncoupling. In this project, the molecular mechanisms of eNOS-uncoupling will be further explored. In addition, the translation will be made to other cardiovascular disorders in which there is evidence of increased oxidative stress as chemotherapy-induced heart failure ind ischemic cardiomyopathy.

                        Researcher(s)

                        Research team(s)

                        Exercise training in chronic heart failure: effects on progenitor cell recruitment and impact on peripheral endothelial function and skeletal muscle. 01/10/2007 - 30/09/2012

                        Abstract

                        The objectives of the project are 1. To study the effects of an acute exercise bout and exercise training (ET versus CT) in CHF patients on recruitment and function of EPC, modulating factors (inflammation, oxidative stress, NO, homing) and functional tests (exercise capacity, endothelial function) 2. To study the effect of exercise training (ET versus CT) in CHF patients on the presence of SPC in the skeletal muscle, skeletal muscle mass, modulating factors and functional tests

                        Researcher(s)

                        Research team(s)

                          Study of the vulnerable atherosclerotic plaque rich in microvessels with immunohistology and 64 detector CT angiography. 01/10/2007 - 30/09/2009

                          Abstract

                          Researcher(s)

                          Research team(s)

                          Expression of vascular adhesion molecules on endothelial progenitor cells and their relation to the homing capacity of these cells towards sites of tissue ischemia. 01/10/2007 - 30/09/2009

                          Abstract

                          This project proposal aims at verifying in which way the different homing signals originating from ischemic tissue lead endothelial progenitor cells - via induction of the PI3K-Akt-eNOS pathway - to express cellular adhesion molecules, which results in efficient homing, adhesion and diapedesis.

                          Researcher(s)

                          Research team(s)

                            Project website

                            Oxidative stress and inflammation: critical role in cardiovascular and infectious diseases. 01/07/2007 - 30/06/2011

                            Abstract

                            Oxidative stress is a pivotal factor in inflammatory processes, but research is hampered by the difficulties to detect free radicals, i.e. reactive oxygen species (ROS) and nitric oxide (NO¿). Objectives of this project include: 1/ validation of methods for in vitro quantification of ROS and NO¿ using electron paramagnetic resonance (EPR); 2/ visualisation of their cellular origin using modern microscopic imaging and 3/ application of these novel platforms to study ROS in inflammatory processes with focus on macrophage function, intracellular infections, atherosclerosis and heart failure.

                            Researcher(s)

                            Research team(s)

                              Blood endothelium progenitor cells and dendritic cells as novel predictive biomarkers of in-stent restenosis after percutaneous coronary intervention. 01/01/2007 - 31/12/2009

                              Abstract

                              The main objective of the present project is to identify blood EPC and DC as novel predictive biomarkers of in-stent restenosis that can be used for developing of a more cost-effective provisional use of DES. This will be evaluated in a longitudinal, prospective observational clinical study in 250 consecutive patients who undergo elective PCI with a bare metal stent (Prokinetic) at the University Hospital of Antwerp.

                              Researcher(s)

                              Research team(s)

                                Effect of exercise on mobilisation and function of endothelial progenitor cells in chronic heart failure. 01/10/2006 - 30/09/2008

                                Abstract

                                In this study, the effect of exercise on the number and function of circulating endothelial progenitor cells (EPC), is evaluated in chronic heart failure patients. A single bout of maximal exercise as well as a physical training program are investigated as stimuli for the release of EPC. Underlying physiological mechanisms are assessed and special attention goes to homing factors, nitric oxide and oxidative stress. Healthy subjects and patients with coronary artery disease will serve as a control group.

                                Researcher(s)

                                Research team(s)

                                  Involvement of nitric oxide pathway in activating endothelial progenitor cells towards homing after myodardial ischaemia. 01/01/2006 - 31/12/2009

                                  Abstract

                                  Researcher(s)

                                  Research team(s)

                                    Study of the vulnerable atherosclerotic plaque rich in microvessels with immunohistology and 64 detector CT angiography. 01/10/2005 - 30/09/2007

                                    Abstract

                                    Researcher(s)

                                    Research team(s)

                                    Functional analysis of potassium channel mutations underlying the long QT syndrome. 01/10/2005 - 30/09/2007

                                    Abstract

                                    Torsade de pointes (Tdp ), one of the most feared cardiac arrythmias is associated with QT prolongation on surface Ecg. This disease already known for some years as long QT syndrome (LQTS) is caused by underlying acquired or congenital disturbances in myocardial transmembrane ion channels causing action potential duration (APD) prolongation. At least six loci (LQTl-6) have already been identified causing congenital LQTS. Although a widespread variety of drugs have QT prolonging properties, many underlying causes for acquired LQTS still have to be identified. Moreover at the level of the cardiac ion channels many biophysical, cell biological and pharmacological mechanisms underlying QT prolongation stili remain unclear. Therefor, the purpose of this research is to study the electrophysiological characteristics of LQT-related cardiac ion channels and the cell biological processes necessary for functional expression to identify the pathogenesis of both acquired and congenital LQTS. The studies are conducted through Whole cell Patch Clamp techniques and if necessary during pharmacological incubation. Confocal microscopy is used to study possible trafficking deficiencies in LQTS.

                                    Researcher(s)

                                    Research team(s)

                                    Coronary hemodynamics after a myocardial infarction. 01/10/2005 - 30/09/2007

                                    Abstract

                                    Cardiovascular morbidity and mortality is one of the major health issues in the Western world. It is known that myocardial infarction can severely affect the prognosis of a patient. More research in this area is needed. Miniaturisation of the technology has made it possible to perform measurements in the human coronary circulation. This technological development offers an unique opportunity to study pathophysiological processes in humans. The vasoreactivity of the microcirculation can for instance be assessed by measuring the flow in basal and hyperemic conditions. Furthermore it is possible to perform simultaneous pressure-flow measurements. With the use of adapted software these signals can be combined and a pressure-flow loop of the coronary circulation can be made. Extrapolation of the diastolic pressure-flowrelation to the pressure-axis (X-axis) can give us an estimation of the zero flow pressure. The slope of this diastolic relation can also learn us something about the conductance of the coronary circulation. Nowadays one has realised that myocardial infarction triggers an inflammatory cascade which is accompanied by the release of numerous cytokines. Their prognostic implications can no longer be denied. The mechanisms that relate acute phase proteins to short and long term prognosis are unclear. New data suggest that impairment of the endothelial function by an inflammatory response creates a link between systemic inflammation and ischemic coronary syndromes. The purpose of this project is to gain more insight in the pathophysiology of the coronary circulation after infarction by perfoming intracoronary measurements and by measuring inflammatory cytokines.

                                    Researcher(s)

                                    Research team(s)

                                      Non invasive assessment of diastolic heart function: Doppler echocardiography and cardiovascular magnetic resonance. 01/10/2003 - 30/09/2005

                                      Abstract

                                      The thesis studies the capability of cardiovascular magnetic resonance to assess global and regional diastolic function using velocity encoding of both myocardial tissue and intracavitary flow. Filling parameters at rest and the impact of stress conditions (loading manipulations and b-adrenergic stimulation) will be analyzed and compared with Doppler.

                                      Researcher(s)

                                      Research team(s)

                                        Functional analysis of potassium channel mutations underlying the long QT syndrome. 01/10/2003 - 30/09/2005

                                        Abstract

                                        Torsade de pointes (Tdp ), one of the most feared cardiac arrythmias is associated with QT prolongation on surface Ecg. This disease already known for some years as long QT syndrome (LQTS) is caused by underlying acquired or congenital disturbances in myocardial transmembrane ion channels causing action potential duration (APD) prolongation. At least six loci (LQTl-6) have already been identified causing congenital LQTS. Although a widespread variety of drugs have QT prolonging properties, many underlying causes for acquired LQTS still have to be identified. Moreover at the level of the cardiac ion channels many biophysical, cell biological and pharmacological mechanisms underlying QT prolongation stili remain unclear. Therefor, the purpose of this research is to study the electrophysiological characteristics of LQT-related cardiac ion channels and the cell biological processes necessary for functional expression to identify the pathogenesis of both acquired and congenital LQTS. The studies are conducted through Whole cell Patch Clamp techniques and if necessary during pharmacological incubation. Confocal microscopy is used to study possible trafficking deficiencies in LQTS.

                                        Researcher(s)

                                        Research team(s)

                                        Coronary hemodynamics after a myocardial infarction. 01/10/2003 - 30/09/2005

                                        Abstract

                                        Cardiovascular morbidity and mortality is one of the major health issues in the Western world. It is known that myocardial infarction can severely affect the prognosis of a patient. More research in this area is needed. Miniaturisation of the technology has made it possible to perform measurements in the human coronary circulation. This technological development offers an unique opportunity to study pathophysiological processes in humans. The vasoreactivity of the microcirculation can for instance be assessed by measuring the flow in basal and hyperemic conditions. Furthermore it is possible to perform simultaneous pressure-flow measurements. With the use of adapted software these signals can be combined and a pressure-flow loop of the coronary circulation can be made. Extrapolation of the diastolic pressure-flowrelation to the pressure-axis (X-axis) can give us an estimation of the zero flow pressure. The slope of this diastolic relation can also learn us something about the conductance of the coronary circulation. Nowadays one has realised that myocardial infarction triggers an inflammatory cascade which is accompanied by the release of numerous cytokines. Their prognostic implications can no longer be denied. The mechanisms that relate acute phase proteins to short and long term prognosis are unclear. New data suggest that impairment of the endothelial function by an inflammatory response creates a link between systemic inflammation and ischemic coronary syndromes. The purpose of this project is to gain more insight in the pathophysiology of the coronary circulation after infarction by perfoming intracoronary measurements and by measuring inflammatory cytokines.

                                        Researcher(s)

                                        Research team(s)

                                          Development, farmacokinetic, in-vitro and in-vivo evaluation of 'multi-component', directly coated drug eluting stents 01/01/2003 - 31/12/2004

                                          Abstract

                                          In-stent restenosis remains a limitation of the percutaneous treatment modalities of coronary atherosclerosis. This project aims to develop 'single-component' and 'multi-component' directly coated drug eluting stents. Selective modulation of oxidative stress, smooth muscle cell migration and proliferation and endothelial cell regeneration are investigated, by single molecules, or combinations of locally delivered molecules. The used methodology consists of stenttechnology, farmacokinetic evaluations, in-vitro and in-vivo biological research.

                                          Researcher(s)

                                          Research team(s)

                                            Coronary hemodynamics after a myocardial infarction. 01/10/2002 - 30/09/2003

                                            Abstract

                                            Researcher(s)

                                            Research team(s)

                                              Coronary flow after acute myocardial infarction : role of cytokine induced endothelial dysfunction and alfa-adrenergic coronary vasoconstriction. 01/01/2002 - 31/12/2005

                                              Abstract

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                                              Research team(s)

                                                Medtronic experiment Cytochalasin D coated stents. 01/11/2001 - 30/10/2002

                                                Abstract

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                                                  Scientific research cardiology unit. 15/09/2000 - 31/12/2000

                                                  Abstract

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                                                    Investigation on the presence of Chlamydia Pneumoniae in human atherosclerotic lesions. 01/01/1999 - 31/12/2000

                                                    Abstract

                                                    Search for the presence of Chlamydia Pneumoniae in patients with atherosclerotic lesions or aneurysmal disease of the aorta, coronary, carotid and femoral arteries and in control vessels without lesions by improved culture techniques and PCR. The PCR will be performed after different DNA extraction methods and in two different laboratories to exclude false positive results.

                                                    Researcher(s)

                                                    Research team(s)

                                                      Local drug application to induce smooth muscle cell paralysis as therapeutic approach to prevent restenosis. 01/01/1998 - 31/12/2001

                                                      Abstract

                                                      Local manipulation of the actin filaments of the smooth muscle cytoskeleton to reduce intimal thickening, constrictive remodeling and changes in contractility in rabbit models of restenosis. We try to detect doses of phallacin, phalloidin and cytoclalasins B and D which interact with actin filaments upon local peri- or intravascular application, which are not lethal for rabbits.

                                                      Researcher(s)

                                                      Research team(s)

                                                        Endothelial dysfunction and intimal proliferation in coronary artery disease and in restenosis after coronary angioplasty and/or stenting. 01/12/1997 - 30/11/1998

                                                        Abstract

                                                        The endothelium plays an important role in the regulation of coronary artery tone and inhibits the proliferation of subintimal vascular smooth muscle cells. Proliferation of the latter contributes to the development of coronary restenosis after balloon angioplasty and/or stenting. The research is focused on methods for the restoration of endothelial function. New therapies aiming at the prevention of coronary restenosis. are evaluated both in experimental animal models and in clinical patients.

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                                                          01/07/1997 - 30/06/1998

                                                          Abstract

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                                                            Cardiac pump function. Basic research on cardiac physiopathology, resulting from clinical observations and leading to clinical applications. 01/01/1997 - 31/12/2000

                                                            Abstract

                                                            The project is aimed at better understanding cardiac pump function in order to refine clinical decision making and therapeutic strategies. It includes research on the intact ejecting heart of anesthetized rabbits, hemodynamic observations in the catheterisation laboratory and in the perioperative setting. Research subjects are: 1. inotropic effects of nitric oxid 2. physiological regulation of left ventricular compliance 3. assessment of cardiac function with the "systolic pressure - relaxation" relationship.

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                                                              01/10/1991 - 30/09/1992

                                                              Abstract

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