Project 2

Experimental interventional cardiology, vascular injury and repair

This interdisciplinary project focuses on device-based percutaneous interventions in the treatment of arteries (coronary and peripheral) and their target tissues in health and disease.

Specifically, we study the following:
1) Pathophysiology of arterial thrombosis in acute ischemic syndromes such as stroke and myocardial infarction. This work is performed in collaboration with projects 13 and 15.
2) The sequelae of - and novel treatment strategies against- ischemia and reperfusion injury in the depending tissues e.g. using biomaterials. This work is performed in collaboration with project 1, and part of the inter-university consortium hDMT. 
3) Pharmacokinetics and -dynamics of systemic and device-based pharmacologic interventions of micro- and macro-vasculature, and modeling of transport phenomena of pharmaca, peptides, proteins and lipids in the arterial wall and atherosclerotic plaque.
4) The role of novel imaging methods (invasive and non-invasive) to assess pathophysiology of arterial thrombosis and treatment effects over time.

Ad 1): The pathophysiology of arterial thrombosis in acute ischemic syndromes is studied in collaboration with the clinical cardiac catheterization laboratory, the dept. of Hematology and the depts. of Neurology and Radiology. This has resulted in three biobank projects, one for coronary thrombus aspirates (CorTAsK project) and two for stroke emboli (MR CLEAN and CONTRAST biobank). Aims are, amongst others, to study how thrombus phenotype affects vascular healing, how it plays a role in no-reflow following reperfusion, and how thrombi can be efficiently and optimally removed from the circulation.

Ad 2): We study the sequelae of - and novel treatment strategies against- ischemia and reperfusion injury in various ways. Committed to replace, reduce and refine animal experiments, we employ ex-vivo vascular models where possible such as healthy and diseased cadaver arteries with heart-lung machines, organ-baths and lab-on-a-chip (microfluidic device) approaches. In addition, we employ a wide range of different disease models in large animals, ranging from simple interventions in healthy young animals to complex dedicated models such as diet- phenotype and/or diabetes induced accelerated atherosclerosis. These are used to unravel important mechanics, pharmacology and pathophysiology of the response to vascular injury and repair in different arterial beds.

Ad 3): Systemic and device-based (pharmacological) interventions are performed in different species and disease models, testing various drug-eluting stents, scaffolds and other intravascular devices. In addition to conventional analysis for safety and efficacy, we study their effects on micro- and macro-vasculature. In collaboration with TU Delft we are modelling transport phenomena of drugs, peptides, proteins and lipids in health and disease. We use routine and spectral histology such as mass spectrometry (MS) imaging (financed by ZonMw through grants to van Beusekom) to study which stent is the best for which patient and to analyze the tissues at high spatial resolution both quantitatively and qualitatively.

Ad 4): We study the diagnostic value of a number of imaging modalities (e.g. OCT, NIRS, IVUS, MSCT and MRI) in order to understand how they can help in characterizing the arterial lesions to study the response of the vasculature itself as well as the effects on the depending tissues. Again, this is aimed at allowing longitudinal pathophysiologic studies and at reducing the number of animals needed.

Principal InvestigatorsHMM van Beusekom, DJGM Duncker, ES Regar 
Co-InvestigatorsPC Burgers, AHJ Danser, DWJ Dippel, ACGM van Es, A van der Lugt, TM Luider, MPM de Maat, G van Soest, F Zijlstra
PhD candidatesASA Autar, H Hund, A Taha