Cardiovascular pathology

Cardiovascular inflammation 

Inflammation of the cardiovascular system is a central denominator in cardiovascular disease. Inflammation not only is an important cause of cardiovascular disease in general, but at the same time cardiovascular diseases activate inflammation. A large body of evidence shows that inflammatory responses to a large extent determine the outcome of many cardiovascular disorders. As such, inflammatory mediators form attractive diagnostic and prognostic biomarkers for the disease process and for monitoring therapeutic interventions, as well as therapeutic targets to prevent or improve the outcome of cardiovascular disease. 
The purpose of our research efforts is to identify and unravel inflammatory processes that underlie and propagate dysfunction of the heart, especially in myocardial infarction and myocarditis. We are studying the pathophysiologic role of these processes both in the myocardium and the cardiac vasculature. In addition, we try to develop diagnostic and prognostic biomarkers that improve the diagnosis of different cardiovascular diseases and that guide and improve therapy. Lastly, we study the efficacy of different anti-inflammatory and immunomodulatory therapies, including enhanced ultrasound-guided mesenchymal stem cell therapy (i.e. StemBell therapy), both to prevent cardiovascular disease and to improve its outcome. Together, these research efforts are aimed to improve diagnosis and treatment and thereby the quality of life for people with cardiovascular disease.
To do this we evaluate inflammatory mediators and inflammatory cell behavior in cardiovascular disease in human tissue banks, in different animal models in vivo and in immune cells, endothelial cells, smooth muscle cells and cardiomyocytes in vitro. The human tissue bank includes autopsied hearts with myocardial infarction of different duration, infectious and non-infectious myocarditis and dilated-, hypertrophic and arrhythmogenic cardiomyopathies; autopsied atherosclerotic coronary arteries, heart valves and atria; and surgical endomyocardial biopsies of myocarditis and heart failure patients, atrial appendices of patients with atrial fibrillation. We attempt to investigate how the local (heart) and systemic (blood, spleen and bone marrow) inflammatory responses lead to and associate with outcomes such as heart failure and sudden death through cardiac arrhythmias, myocardial infarction and myocarditis. Moreover, we evaluate inhibitors of these mediators as proof-of-principle in animal models in vivo. These include the immunomodulating and tissue regenerative effects of the in-house developed ultrasound-guided adipose tissue-derived mesenchymal stem cells.

Staff / post-doc / promovendi / students projects

Hans Niessen MD PhD  - program leader 
Paul Krijnen MD PhD    - program leader


Ellis ter Horst


Amber van Broekhoven
Linghe Wu
Ibrahim Korkmaz 
Amber Korn

Students projects

StemBell therapy for immunomodulation in cardiovascular disease
Inflammation, the response of the immune system on microbial infection and/or tissue damage, plays a crucial role in the pathogenesis of many cardiovascular diseases. Moreover, inflammation is an important denominator of the outcome of among others atherosclerosis, myocardial infarction and viral myocarditis. In the Cardiovascular Pathology research group we try to unravel the role of different inflammatory processes in the pathogenesis of these disorders and we try to improve their outcome by targeting these processes with therapeutic intervention.  
In this project the student will focus on the therapeutic mechanisms of StemBell therapy in atherosclerosis, myocardial infarction and viral myocarditis. In StemBell therapy, stem cells are targeted to areas of interest using ultrasound. The student will investigate local and systemic immunomodulating effects of stem cells, especially those generated through the secretion of cell protective and immunomodulating factors, i.e. the paracrine effect. 
Techniques: Cell culture, tissue culture, histochemistry, immunohistochemistry, ELISA, flow cytometry. 

Cardiac depressive effects in viral myocarditis
In viral myocarditis the heart is infected by a cardiotropic virus, which in turn triggers an immune response in the heart. In most deceased patients with viral myocarditis the damage to the heart is found to be very limited. This offers the question of why these people suffer from acute loss of heart function and even death. The most likely hypothesis is that the apparent undamaged myocardium is not functioning properly. In the Cardiovascular Pathology research group we have found clues that cardiomyocytes in the undamaged myocardium show signs of stress and altered gene expression, that may underlie their dysfunction.
In this project the student will focus on further unraveling these changes in cardiomyocytes in the undamaged myocardium in viral myocarditis and how they may relate to cardiac dysfunction. These studies will be performed in autopsied hearts of viral myocarditis patients and in an animal model of viral myocarditis. 
Techniques: histochemistry, immunohistochemistry, cell culture, tissue culture, PCR, Western blot, flow cytometry.