Masterstudent Research projects Department of Social Medicine, AMC
In our department we provide a MSc research project of minimally 4 months (longer is preferred). A brief description of the available project is listed below:
1. Ideal cardiovascular health in early childhood and cardiometabolic outcomes in pre-adolescence
Dr. T.G.M. Vrijkotte and B.A. Hutte
In 2010 the American Heart Association (AHA) released its 2020 impact goals that highlighted primordial prevention. One of the impact goals was, ‘’to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%’’. This goal should be achieved by helping the general population move towards ‘ideal cardiovascular health’ by focusing on seven metrics (Mets): smoking, physical activity, dietary patterns, blood
pressure, glucose and cholesterol levels and body mass index (BMI)1. These seven factors are classified into three categories: ideal, intermediate and poor. Individuals with ideal levels for all seven metrics are considered to have ideal cardiovascular health (ICH). Recently, several studies have been published concerning the individual associations between the seven metrics of ICH in childhood and the development of cardiometabolic outcomes in adulthood 3-10. Findings of a study
of Laitinen et al (2012), showed for the first time that an increased number of ICH metrics present in childhood was associated with reduced risk of hypertension and metabolic syndrome. Another important finding from this cohort was that most of the children and young adults with optimal ICH status at young age, lost this status before reaching middle age11. However, studies concerning ICH and its relationship with cardiometabolic outcomes at younger ages are lacking. Therefore, we aim to study the association between ICH in early childhood and cardiometabolic outcomes in adolescence.
Research question: To what extent is ICH at age 5/6 associated with cardiometabolic outcomes at age 11/12 years?
Analysis plan: ICH at age 5 will be based on 6 metrics (smoking status is not relevant at this age) available from the health check at age 5, a food frequency questionnaire and a questionnaire about physical activity of the child filled in by the mother. Considered cardiometabolic outcomes at age 11/12 years will be: blood pressure, lipids, glucose, body composition and carotid intima-media thickness which is an validate surrogate marker of CVD risk and all-cause mortality2. We will explore the association between ICH in early childhood and cardiometabolic outcomes in adolescence by means of linear regression analyses. Potential confounders (SES, ethnicity, puberty) will be considered using multivariable models.
Masterstudent Research projects Department of Anesthesiology, AMC
In our department we provide MSc research projects of minimally 6 months. Students are supervised by the PI and participate in departmental scientific meetings and Journal clubs. A brief description of the available projects is listed below:
1. Novel and optimal multimodal therapy against acute myocardial infarction
Acute myocardial infarction (AMI) remains one of the common causes of death and hospitalization worldwide. Improved treatment strategies for AMI are urgently needed for for the prevention of adverse cardiac remodeling and eventual heart failure. In this research line we explore several novel and high potential targets against acute infarction and combine
them to gain maximal reductions in infarct size in animal studies, with a keen eye towards applicability towards the clinical arena.
Techniques: isolated perfused mouse hearts, in vivo cardiac infarction model rat, stabile isotope for cardiac metabolism, cell death parameter analysis, western blotting, spectrophotometric enzyme analysis.
2. Unravelling the mechanisms of the effective diabetes medicine Empagliflozin
Dr. Coert J Zuurbier, Dr. Nina C Weber
The kidney-targeted Empagliflozin (EMPA) caused a large reduction in heart failure hospitalization and cardiovascular death in diabetes patients (Zinman B et al, NEJM 2015). Surprisingly, the underlying mechanisms are largely unknown. In this project we try to unravel the cellular mechanisms and actions of empagliflozin in the heart and endothelial cell.
Techniques: isolated perfused mouse hearts, isolated endothelial cells, stabile isotope for cardiac metabolism, genetic
manipulations of targeted genes, cell culture, cell physiology parameter analysis, western blotting, spectrophotometric enzyme analysis.
Master student Research projects Department of Medical Biochemistry, AMC
In our department we provide MSc research projects of minimally 6 months. Students are supervised by dedicated scientists and participate in departmental scientific meetings and Journal clubs. A brief description of the available projects is listed below:
1. Aortic Aneurysms: how to predict them and how to inhibit further dilatation.
Aortic aneurysms are dilatations of the aorta, which result in prophylactic aortic surgery when the aneurysm grows beyond 5 cm in diameter. In Marfan Syndrome patients, aortic aneurysm growth and rupture is the main cause of mortality. It is difficult to predict which patient is at high risk of aneurysm development and rupture. We study aortic markers in human and Marfan mouse aortic tissue, to develop predictive tools for aneurysm growth and rupture. Moreover, we perform intervention studies in a Marfan mouse model to reveal new therapeutic approaches.
Techniques: cell culture vascular cells, histological analyses Marfan mice, mouse experiments treating Marfan mice.
2. Nuclear Receptor Nur77 reduces the inflammatory response of macrophages
The orphan nuclear receptor Nur77 (NR4A1) regulates a large variety of cellular processes and macrophage inflammatory signaling. We study Nur77-mediated gene regulation by comparing genome-wide DNA binding (ChIP-seq) and gene expression profiles (RNA-seq) in RAW264.7 macrophages. In this research project the bioinformatic analyses of databases provide novel clues on the role of Nur77 in macrophages, which will be explored in follow up experiments.
Techniques: bioinformatics, cell culture macrophages (mouse, human, cell lines), gain-of-function and knockdown experiments, RNA/protein expression, Seahorse metabolism assays.
3. Molecular regulation of lipid metabolism by LXRs and the ubiquitin proteasomal system
We are interested in elucidating the molecular mechanisms that govern cellular and whole-body lipid metabolism. Specifically, we focus on the role of the ubiquitin-proteasomal-system and of the nuclear receptors LXRs herein. We have identified several new genes that play a role in controlling sterol and fatty acid metabolism in cells and are using biochemical, cellular biological, and mouse models to investigate their function. In particular, we are aiming to understand the role of these genes in cardiovascular and metabolic disease.
Techniques: Culture of primary cells and cell lines, Genetic manipulation of cells and mice using CRISPR/Cas9- and transfection-based methodology, Molecular biology, Biochemical assays, functional genetic screens.
4. Macrophage regulation in cardiovascular disease
We are interested in the regulation of macrophages in cardiovascular diseases. Using a combination of patient materials, human and mouse cellular models and mouse in vivo studies we are identifying pathways that regulate macrophages in disease. We are particularly interested in how settings of low-grade inflammation, dyslipidemia and atherosclerosis affect the molecular repertoire of monocytes and macrophages through metabolic and epigenetic processes.
Techniques: Cell culture, Gene expression, Epigenetics, FACS, Bioinformatics, Seahorse metabolism assays, Biochemicical and molecular assays.
5. Immune cell interactions in atherosclerosis and obesity
We are interested in how immune cells talk to each other in cardiovascular disease and in obesity. We are particularly interested in one group of immune modulators: the immune checkpoint regulators. Using a combination of mouse models, cell culture models, FACS analysis, histology and western blotting, we are identifying pathways how immune checkpoint regulators and co-stimulatory molecules in particular drive atherosclerosis and obesity. Based on these pathways, we design and test small molecule inhibitors to treat atherosclerosis.
Techniques: Histology, Microscopy, Cell culture, Gene expression, FACS, Bioinformatics, Biochemicical and molecular assays.
6. Vascular Microenvironment and Integrity
We are interested in understanding how endothelial cells respond to mechanical changes induced by physiological dynamics taking place within the vessel wall. In particular we search for novel molecular events taking place at endothelial cell-cell junctions (VE-cadherin complex) and cell-extracellular matrix adhesions (integrin complexes). These are crucial structures that preserve vascular barrier function, and are tightly controlled during vascular development, angiogenesis and transendothelial migration of inflammatory cells. More information about the research: www.huveneerslab.eu
Techniques: Live fluorescence microscopy, endothelial cell culture, image analysis, shRNA-mediated knockdowns, biomechanical assays and biochemistry.
Masterstudent project in department of Radiology, AMC
For duration and conditions of the project contact the principal Investigator.
1. Clinical implementation of state-of-the-art 4D flow MRI for cardiovascular diagnostics
Dr. R.N. Planken, AMC, room C1-210, Phone: +31-20-5661184, Pager: 81 59680
4D flow MRI is an advanced non-invasive technique for visualization of blood flow. Clinical implementation of this technique is innovative and provides new insights into the function of heart valves, heart chambers and major blood vessels. This technique is particularly promising for the investigation of heart valve dysfunction.
This project focuses on the clinical implementation of 4D flow MRI. The candidate will specialize in 4D flow MRI (both scanning and post processing). With this knowledge and skills the candidate will conduct studies on the clinical value of 4D flow MRI in the context of mitral regurgitation.
Master student research projects department of Pathology, AMC
In our department we provide MSc research projects of minimally 5 months. Students are supervised by dedicated scientists and participate in departmental scientific meetings and Journal clubs. A brief description of the available project is listed below:
The Heart-Brain connection
In our research group we are interested in the connection between the heart and the brain. Despite the capacity of the brain to adapt cerebral blood flow to its own demand, systemic hemodynamic changes such as the function of heart, aorta and cerebral arteries may reflect on the cognitive functioning. In this project we study the molecular regulation of (extra- and intra-cranial) endothelial cells in protecting the brain against hemodynamic changes to understand their function in cardiovascular induced brain pathologies.
Techniques: We perform immunohistochemistry and imaging combined with quantitative molecular techniques.
Master student projects of the Department of Cardiology, AMC
Please contact the Principal Investigator for duration and conditions of the projects.
1. The effect of CTO PCI in STEMI patients on right ventricular function.
Prof. dr. J.P.S. Henriques / Drs. J. Elias
RV dysfunction after STEMI has been shown to be relatively common . In most cases, the RV recovers its function during the post STEMI period. Furthermore the RV recovers more rapidly and to a greater extent as compared to LV function. However, RV dysfunction have been shown to have an effect of long term outcomes. CMR can be used to identify and quantify RV dysfunction. RV ejection fraction (RVEF), T2-weighted imaging, as well as late gadolinium enhancement (LGE) imaging have all been used to assess RV function. Therefore in this EXPLORE CMR substudy we will use CMR to gain insight on the impact of CTO PCI compared to no-CTO PCI on right ventricular recovery (comparing baseline to 4 month FU) and correlating it with clinical and angiographic variables.
Techniques: CMR analysis: cine imaging, late enhancement, analysis of STEMI patient data, clinical translation.
2. The effect of revascularization of a CTO on ECG parameters reflecting depolarization and repolarization in STEMI patients.
Prof. dr. J.P.S. Henriques / Drs. IM van Dongen
Observational studies have shown a beneficial effect of percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) on survival in stable patients. The etiology of this survival is unknown. This could be due to an improvement in the left ventricular function reducing the occurrence of heart failure, and/or as a result of electrical stabilization which reduces the occurrence of ventricular arrhythmias associated with sudden cardiac death. In the VACTO-PRIMARY study patients with a CTO showed to have more ventricular arrhythmias and received more appropriate ICD therapy, underscoring the theory that CTO patients experience more electrical instability. In this research project we want to investigate the effect over time of CTO-PCI on several ECG parameters that reflect the cardiac electrophysiology, compared to patients that do not receive CTO-PCI. Additionally, we want to investigate the correlation of these ECG parameters with the occurrence of clinical events.
Techniques: ECG analysis, ECG interpretation, patient data analysis and interpretation, clinical translation.
3. Analysis of the arterial blood pressure curve in cardiogenic shock complicating myocardial infarction.
Prof. dr. J.P.S. Henriques / D.M. Ouweneel MSc.
Cardiogenic shock (CS) is the most common cause of death in patients with an acute myocardial infarction. Cardiogenic shock is a gradual phenomenon, manifesting in different forms, from mild to severe shock. Currently, there is no classification system to objectively grade cardiogenic shock. Ideally, a cardiogenic shock grade would appropriately classify the depth and it is likely that various therapies would be adjusted accordingly. In CS the decrease of cardiac performance and consequent decrease of blood pressure causes inadequate perfusion pressure. Blood pressure plays a central role in the definition of CS. Since arterial blood pressure is mainly determined by both heart and vasculature, its components or morphology may have a key role in the search for a cardiogenic shock grading. It is aimed to create an objective grading for cardiogenic shock based on the morphology of the blood pressure curve. Different blood pressure curve parameters (such as the height, slopes and inflection points) are analyzed before and after treatment with percutaneous intervention (PCI) and after PCI. Arterial pressure curve parameter are compared between CS and non-CS patients and between survival -and non-survival groups.
Techniques: Arterial pressure curve analysis, STEMI patient data analysis and interpretation, Nexfin blood pressure measurements.
4. Computed tomography coronary angiograpy instead of invasive coronary angiography in selected patients.
Prof. dr. J.P.S. Henriques / Dr. B.E.P.M. Claessen / Dr. M.A.M. Beijk / Dr. R.N. Plancken
Invasive coronary angiography is the gold standard to diagnose obstructive coronary artery disease. Computed tomography coronary angiography using modern multi-slice multi-detector CT scanners is an alternative imaging technique that can be used to rule out significant coronary stenoses which is associated with less complications, contrast use, patient anxiety and costs. Patients at a low a priori risk for obstructive coronary artery disease such as patients awaiting cardiac valve surgery and patients with ventricular tachycardias or reduced left ventricular function with no history of anginal complaints or coronary artery disease will undergo CT coronary angiography followed only by invasive angiography if the CT scan suggests the presence of stenosis. Outcome measures include diagnostic yield of CT coronary angiography, correlation of CT angiography imaging and computational fluid dynamics with invasive coronary imaging and invasive FFR measurements, and cost-effectiveness.
Techniques: CT coronary angiography, invasive coronary angiography, computational fluid dynamics and fractional flow reserve, cost-effectiveness analysis.
5. AMC VA-ExtraCorporeal Life Support program.
Prof. dr. J.P.S. Henriques / Dr. K.D. Sjauw / Drs. D.M. Ouweneel / Dr. R. Koster.
The use of extracorporeal life support (ECLS), c.q. extracorporeal membrane oxygenation (ECMO) for adult patients in acute cardiopulmonary arrest is increasing, both in the setting of cardiac arrest (eCPR) and the setting of cardiogenic shock. A recent meta-analysis from our group showed that immediate initiation of ECMO yields in better survival compared with conventional therapy, especially in cardiac arrest but also in severe cardiogenic shock. Extracorporeal cardiopulmonary resuscitation (eCPR) has been proposed as ideal for patients in refractory cardiac arrest failing conventional cardiopulmonary resuscitation (CPR). We will investigate the feasibility of immediate ECMO in both the setting of cardiac arrest (Part 1) and cardiogenic shock (Part 2).
Techniques: Collaboration in development of study/trial protocol. Collaboration in development of regional (Groot Amsterdam/Noord-Holland) rapid-response ECMO cardiac arrest chain-of-survival protocol/infrastructure. Cardiac arrest and cardiogenic shock patient data retrieval, analysis and interpretation. Several hemodynamic measurements (i.e. intracoronary physiology, microcirculation, systemic circulatory measurements during ECMO support).
Masterstudent project in department of Biomedical Engineering and Physics, AMC
For duration and conditions of the project contact the principal Investigator.
1. Development of a rat model for silent brain infarcts
Brain infarcts have overt and devastating consequences. However, small infarcts may occur much more frequently with aging and several cardiovascular diseases, and remain relatively unnoticed. We speculate that accumulation of small infarcts ultimately leads to cognitive impairment. In this project the student will help to develop a rat model for small infarcts by infusing microspheres into the cerebral circulation. Capillary perfusion is analyzed post mortem from brain sections. Potential recovery is studied by comparison of perfusion at day 1, day 7, and day 28 after microsphere infusion.
Techniques: Surgery, histology, 3D capillary analysis, immunohistochemistry.