The department of Experimental Vascular Medicine focuses on basal and translational research in cardiometabolic diseases. The overall aim is to understand the (epi)genetic, molecular and cellular pathophysiology of these disorders and to translate this knowledge into clinical applications such as diagnostic and prognostic biomarkers and novel treatments.
The department has a strong focus on optimisation of diagnosis and treatment of athero-thrombotic cardiometabolic diseases. The Experimental Vascular Medicine has a long-lasting reputation on early translational research of innovative therapies in humans (gene therapy, antisense, small molecules), surrogate marker studies for cardiovascular disease (ultrasound, MRI, stable isotope fluxes), diagnostic studies (thrombosis/pulmonary embolism) and RCTs in cardiometabolism. The research conducted at the department is done in close collaboration with the Department of Vascular Medicine.
In addition, a dedicated clinical/research program for patients with cardiovascular genetic diseases (lipids, thrombosis, premature atherosclerosis and diabetes) has been implemented. Also, the Microbiota Center Amsterdam (MiCA) is based here. The ambition of the department is to unravel novel mechanisms contributing to cardiometabolic disease, as well as to evaluate novel diagnostic and therapeutic strategies by applying systems medicine and machine learning approaches.
The main research lines comprise the following:
Atherosclerotic vascular disease is a chronic low-grade inflammatory process with a clinically silent period of decades. Abnormalities in the genetics, levels, fluxes and composition of the different lipoproteins are the backbone of the atherosclerosis research line. The development of novel strategies to modify lipoprotein metabolism, to quantify reverse cholesterol transport, to reverse atherosclerosis and prevent cardiovascular disease are an integral part of the atherosclerotic research activity. In parallel, innovative imaging strategies are being evaluated (functional, MRI-applications) to allow for better phenotyping and follow-up of preclinical atherosclerosis.
Obesity and insulin resistance are involved in the development of diabetes mellitus. Current understanding about the pathophysiology of these diseases (including involvement of the intestine and the gutmicrobiota) is limited as well as the role of personalized medicine approaches in developing personalized targeted diagnostics and therapeutics. Our group therefore studied the effect and hierarchy of these factors involved in weight loss (bariatric surgery BARIA cohort in collaboration with the Spaarne hospital, NAFLD-NASH (ANCHOR) cohort and weight gain in the normal population (in collaboration with the Amsterdam HELIUS cohort and Amsterdam diabetes center). Also, the Microbiota Center Amsterdam (MICA) for bioinformatics analyses of gut microbiota sequencing dtata, anaerobic culture facility and autologous fecal transplant bank (AFEBA) are based here.
(Venous) thrombo-embolic diseases provide another key area of research. The regulation of the coagulation system is studied with the goal to identify novel risk factors and targets to prevent/treat venous and arterial thrombosis. Areas of special interest comprise thrombosis in cancer, women’s' issues in thrombosis (pregnancy, pathogenesis) and evaluation of novel anti-thrombotic agents as well as their antidotes.
The research program is conducted by a total of 7 independent project leaders (75 PhD students and 9 postdocs) in close collaboration with a large network of internal, national and international partners. With an output of more than 550 peer-reviewed publications over the last 5 years and very successful external funding, the Department of Experimental Vascular Medicine has gained a broad range of expertise in four main research lines:
Vascular Metabolism, Inflammation and Atherosclerosis
Inflammation of both the endothelium and circulating immune cells play an important role in the progression of atherosclerosis. In the last years it has been shown that alterations in the intracellular metabolism of immune cells, more specifically monocytes, is the driving force behind their inflammatory phenotype. This is important, since mapping this lipid and lipoprotein-induced metabolic reprogramming paves the way for future therapeutic strategies to target and or reverse this metabolic phenotype in order to slow down atherosclerosis.
However, research in the context of vascular metabolism, i.e. the role of metabolic alterations in steering blood vessel inflammation, is still in its infancy. In this line of research we aim to investigate the role of endothelial cell metabolism in driving cardiovascular disease, in order to gain new insight in the crosstalk between this metabolism-driven inflammatory response of the endothelium under hyperlipidemic conditions. In addition, we have a strong focus on optimization of treatment of athero-thrombotic cardiometabolic diseases by performing preclinical pathophysiological research.
Jeffrey Kroon, PhD
Lipid Metabolism and Insulin Resistance
Disturbances in lipid and triglyceride metabolism are a major cause in the increased risk in the development of cardiovascular diseases.
The liver is the key organ in control of plasma lipid concentrations. Elevations in the hepatic lipid content in non-alcoholic fatty liver disease (NAFLD) predispose for cardiovascular diseases. Research in our department has a strong emphasis on NAFLD. At the EVG currently in vivo as well as in vitro methods are being used to explore, amongst others, 1) the role of gut microbial derived metabolites, and 2) the interplay between the different hepatic cell types on NAFLD development. Further research is also focused on known and unknown genes which play a role in the homeostasis of the lipid metabolism and can be dissected in two main research lines: 1) The effects of (functional) mutations in candidate genes and 2) the identification of new genes. To visualize the physiological role of mutations and or novel genes an extensive toolbox of functional tests is available including studies with cultured cells as well as lipid flux measurements using stable isotope based technology. Both research lines are mainly based on the investigation of the incidence of cardiovascular diseases in families at risk. This is feasible by the availability of genetic fieldworkers and nurses who collect the information of the family history and biomaterials at each individual family member. The work is conducted in close collaboration with the department of Vascular Medicine and the LEEFH foundation and the Laboratory Human Genetics.
Proffessors Kees Hovingh, PhD, MD and Erik Stroes, PhD, MD
Onno Holleboom, PhD, MD
Han Levels, PhD and Aldo Grefhorst, PhD
Obesity, Metabolic Syndrome and Type 2 Diabetes
Our group focuses on underlying causal mechanisms in the progression of obesity to type 2 diabetes and its cardiovascular comorbidity. This research line is human centered and conducted using a cohort of bariatric surgery patients (collaboration Spaarne ziekenhuis) and a large multiethnic HELIUS cohort. Computational modelling and machine learning on multi-omics data (integromics) sets is carried out to visualize disease trajectories. Special interest focuses on the role of gutmicrobiota (MiCA) in causing cardiometabolic disease and NAFLD-NASH. We aim to find novel pathophysiological pathways driving dyslipidemia and insulin resistance and their hierarchical clustering in driving chronic adipose tissue, liver and macrovascular inflammation. Identification of novel diagnostic and therapeutic targets (for instance, inhibiting bacterial metabolite production and/or replenishing novel beneficial bacterial strains) may lead to a more personalized medicine treatment for cardiometabolic disease.
Prof. Max Nieuwdorp, PhD, MD
Evgeni Levin, PhD
Hilde Herrema, PhD
Victor Gerdes, PhD, MD
Daniel van Raalte, PhD, MD
Elena Rampanelli, PhD and Nordin Hanssen PhD, MD
Hemostasis and Thrombosis
The blood coagulation system is an essential host defense mechanism. Better insights in blood platelets, the (regulation of the) coagulation system and fibrinolysis have lead and will lead to new risk factors for venous thrombosis and to targets for therapy for venous and arterial thrombosis. In the light of this scope a number of research-lines are being explored.
Prof. Joost Meijers, PhD