Netherlands Heart Foundation
Dr E. Dekker programme: the 2005 winners The Dr E. Dekker programme of the Netherlands Heart Foundation (NHF) is a stimulation programme which contains fellowships for outstanding researchers (clinicians and non-clinicians) in the cardiovascular field. In 2005 the NHF awarded a Dr E. Dekker fellowship to seven researchers. Established Investigators Y.M. Pinto, MD, PhD (University of Maastricht) Title: It is the aged myocardium that fails: does accelerated senescence of cardiac myocytes explain failure of overloaded hearts?
Growth factor signalling provokes cellular senescence to protect against the formation of cancer. Similar growth factor systems are also activated in hypertension and heart failure. This leads to the hypothesis that these systems can also induce senescence in cardiac myocytes. This programme aims to demonstrate that an overloaded myocardium ages rapidly and which ageing mechanisms are involved. This can provide novel clues for treatment and a theoretical basis to introduce anti-senescence compounds into the heart failure field. H. Vink, PhD (University of Amsterdam) Title: The endothelial glycocalyx: first-line defence against cardiovascular disease
Recent studies have demonstrated that the glycocalyx serves as a protective barrier between the endothelium and blood. This research programme addresses the role of the glycocalyx. It explores whether perturbation of the endothelial cell glycocalyx by cardiovascular risk factors contributes to the increased sensitivity of the arterial wall towards atherogenic stimuli, resulting in accelerated formation of atherosclerotic lesions. More insight into this mechanism could provide a possible new target for future prevention strategies. C.R. Bezzina, PhD (University of Amsterdam) Title: In search of genes for cardiac conduction
Almost 20% of deaths in the population are sudden. Of these, the great majority are due to ventricular fibrillation in the context of myocardial infarction. Slowing of conduction of the cardiac electrical impulse plays a critical role in the genesis ofthese arrhythmias. Although twin studies have demonstrated strong genetic effects for cardiac conduction, genes for these effects are largely unknown. This research plan aims to identify genes controlling cardiac conduction. The identification of these genes is expected to improve risk stratification in patients with ischaemic heart disease and open new avenues ofresearch into new therapies. Postdoctoral fellow J.D. van Buul, PhD (Sanquin) Title: The role of endothelial GEFs in the control of barrier function and leukocyte extravasation
The endothelial barrier function controls the traffic of leukocytes from the circulation to the underlying tissue. During cardiovascular events and atherosclerosis, the barrier |)C
Netherlands Heart Journal, Volume 14, Number 3, March 2006
function and leukocyte trafficking across the endothelium are severely affected. Excessive leukocyte adhesion to and traffic through the endothelium result in severe plaque formation. This programme aims to clarify how leukocyte adhesion to and migration through the endothelium are regulated. Finding ways to block this process can contribute to future therapeutic tools to prevent atherosclerosis. M.C.H. de Visser-van Soest, PhD (University of Leiden) Title: Novel genetic risk factors for venous thrombosis. Their identification and the study of their interactions with genes and environment
Venous thrombosis (VT) is a multicausal disease, in which environmental and genetic risk factors are involved and interact. Familial thrombophilia is considered to be an oligogenetic disease, where at least two genetic defects segregate in the famnily. In a large number of these families none or only one of the known genetic risk factors is found. This suggests that genetic risk factors are missing. The aim ofthis programme is to identify novel genes that contribute to the susceptibility to VT. Knowledge ofthese genes will improve individualised risk profiling for VT.
Physician in speciality training Y.M. Ruigrok, MD (University of Utrecht) Title: The role of the extracellular matrix in intracranial aneurysms
A familial preponderance is the strongest risk factor for a subarachnoid haemorrhage from an intracranial aneurysm. This means that genetic factors play an important role. This research project aims to identify candidate genes that are involved in the development of intracranial aneurysms. Knowledge about these genes may yield (bio)markers which can be used for early diagnosis of unruptured aneurysms. Furthermore, identifying the genetic factors will lead to a better understanding of the pathogenesis ofthese aneurysms. This may lead to new therapeutic interventions.
Physician before speciality training L. Timmers, MD (University of Utrecht) Title: Cardiac progenitor cell transplantation as a potential curative therapy for ischemic heart failure
Currently, the treatment of myocardial infarction and heart failure is primarily focused on prevention of further myocardial tissue loss and complications. Curative therapeutic options are basically non-existent. Stem cell therapy may provide a new approach to restore cardiac function after myocardial infarction. Recently discovered cardiac progenitor cells (CPCs) seem to be a promising stem cell source for myocardial regeneration. This study will investigate whether human CPCs differentiate into cardiomyocytes after transplantation and whether they contribute to myocardial regeneration, thereby improving cardiac function. M Nelleke van der Houwen, Netherlands Heart Foundation
117
Dr E. Dekker programme: the 2005 winners The Dr E. Dekker programme of the Netherlands Heart Foundation (NHF) is a stimulation programme which contains fellowships for outstanding researchers (clinicians and non-clinicians) in the cardiovascular field. In 2005 the NHF awarded a Dr E. Dekker fellowship to seven researchers. Established Investigators Y.M. Pinto, MD, PhD (University of Maastricht) Title: It is the aged myocardium that fails: does accelerated senescence of cardiac myocytes explain failure of overloaded hearts?
Growth factor signalling provokes cellular senescence to protect against the formation of cancer. Similar growth factor systems are also activated in hypertension and heart failure. This leads to the hypothesis that these systems can also induce senescence in cardiac myocytes. This programme aims to demonstrate that an overloaded myocardium ages rapidly and which ageing mechanisms are involved. This can provide novel clues for treatment and a theoretical basis to introduce anti-senescence compounds into the heart failure field. H. Vink, PhD (University of Amsterdam) Title: The endothelial glycocalyx: first-line defence against cardiovascular disease
Recent studies have demonstrated that the glycocalyx serves as a protective barrier between the endothelium and blood. This research programme addresses the role of the glycocalyx. It explores whether perturbation of the endothelial cell glycocalyx by cardiovascular risk factors contributes to the increased sensitivity of the arterial wall towards atherogenic stimuli, resulting in accelerated formation of atherosclerotic lesions. More insight into this mechanism could provide a possible new target for future prevention strategies. C.R. Bezzina, PhD (University of Amsterdam) Title: In search of genes for cardiac conduction
Almost 20% of deaths in the population are sudden. Of these, the great majority are due to ventricular fibrillation in the context of myocardial infarction. Slowing of conduction of the cardiac electrical impulse plays a critical role in the genesis ofthese arrhythmias. Although twin studies have demonstrated strong genetic effects for cardiac conduction, genes for these effects are largely unknown. This research plan aims to identify genes controlling cardiac conduction. The identification of these genes is expected to improve risk stratification in patients with ischaemic heart disease and open new avenues ofresearch into new therapies. Postdoctoral fellow J.D. van Buul, PhD (Sanquin) Title: The role of endothelial GEFs in the control of barrier function and leukocyte extravasation
The endothelial barrier function controls the traffic of leukocytes from the circulation to the underlying tissue. During cardiovascular events and atherosclerosis, the barrier |)C
Netherlands Heart Journal, Volume 14, Number 3, March 2006
function and leukocyte trafficking across the endothelium are severely affected. Excessive leukocyte adhesion to and traffic through the endothelium result in severe plaque formation. This programme aims to clarify how leukocyte adhesion to and migration through the endothelium are regulated. Finding ways to block this process can contribute to future therapeutic tools to prevent atherosclerosis. M.C.H. de Visser-van Soest, PhD (University of Leiden) Title: Novel genetic risk factors for venous thrombosis. Their identification and the study of their interactions with genes and environment
Venous thrombosis (VT) is a multicausal disease, in which environmental and genetic risk factors are involved and interact. Familial thrombophilia is considered to be an oligogenetic disease, where at least two genetic defects segregate in the famnily. In a large number of these families none or only one of the known genetic risk factors is found. This suggests that genetic risk factors are missing. The aim ofthis programme is to identify novel genes that contribute to the susceptibility to VT. Knowledge ofthese genes will improve individualised risk profiling for VT.
Physician in speciality training Y.M. Ruigrok, MD (University of Utrecht) Title: The role of the extracellular matrix in intracranial aneurysms
A familial preponderance is the strongest risk factor for a subarachnoid haemorrhage from an intracranial aneurysm. This means that genetic factors play an important role. This research project aims to identify candidate genes that are involved in the development of intracranial aneurysms. Knowledge about these genes may yield (bio)markers which can be used for early diagnosis of unruptured aneurysms. Furthermore, identifying the genetic factors will lead to a better understanding of the pathogenesis ofthese aneurysms. This may lead to new therapeutic interventions.
Physician before speciality training L. Timmers, MD (University of Utrecht) Title: Cardiac progenitor cell transplantation as a potential curative therapy for ischemic heart failure
Currently, the treatment of myocardial infarction and heart failure is primarily focused on prevention of further myocardial tissue loss and complications. Curative therapeutic options are basically non-existent. Stem cell therapy may provide a new approach to restore cardiac function after myocardial infarction. Recently discovered cardiac progenitor cells (CPCs) seem to be a promising stem cell source for myocardial regeneration. This study will investigate whether human CPCs differentiate into cardiomyocytes after transplantation and whether they contribute to myocardial regeneration, thereby improving cardiac function. M Nelleke van der Houwen, Netherlands Heart Foundation
117
