to organ...

to organ...

The projects we work on in research theme 3 were initiated in parent consortium MIIHD. We will further develop diagnostic tools that can be used for initiating personalized treatment of patients at high risk for developing heart disease. We will also work on a novel contrast agent for detecting active thrombus formation.

WP3.1 Frizzled: Novel myofibroblast markers
Work package 3.1
WP3.1 Frizzled: Novel myofibroblast markers

Myofibroblasts in the infarct area can preserve cardiac function after a heart attack. Imaging the myofibroblast content can thus be useful for estimating the risk of heart failure after a myocardial infarction. We want to provide proof of concept of myofibroblast imaging using so called frizzled ligands as markers. We will use different model systems and translate these findings to patient material. Furthermore we will do research to optimize the new diagnostic tool. We aim at using the method for classifying patients into low- and high risk groups for heart failure development.

Figure: Adapted from Laeremans H,  Hackeng TM, van Zandvoort MAMJ, Thijssen VLJL, Janssen BJA, Ottenheijm HCJ, Smits JFM and Blankesteijn WM. Blocking of frizzled signaling with a homologous peptide fragment of Wnt3a/Wnt5a reduces infarct expansion and prevents the development of heart failure after myocardial infarction. Circulation 2011; 124:1626-1635

Work package leader(s): 
Matthijs Blankesteijn, Dr.
Peter Timmerman, Prof. dr.
WP3.2 A novel contrast agent for detecting active thrombus formation in vivo
Work package 3.2
WP3.2 A novel contrast agent for detecting active thrombus formation in vivo

Early detection and fibrinolytic therapy of thrombus formation is crucial for prevention and treatment of stroke. Non-invasive molecular detection of fresh thrombi can greatly aid in localizing sites of occlusion and in clinical descision making. We have shown that bimodal contrast agent A14 can visualize thrombus formation seconds after induction, both in vitro and in vivo (in the mouse). Imaging was specific for fresh thrombi as older thrombi (>24h) were not detected. We will assess and optimize the affinity and specificity of A14-variants and make them suitable for large scale production. We will evaluate the modified peptide in animal studies and prepare for a proof of concept study in men.

Figure: Bimodal molecular imaging of thrombi with A14-DTPA-Gd-rhodamine. Yellow arrows indicate positive in vivo magnetic resonance imaging (MRI) intensity of an FeCl3-induced carotid artery thrombus. Two-photon laser scanning microscopy (TPLSM) reveals elongated smooth muscle cells of the vessel wall (green) together with leucocytes (green) captured in the thrombus visible by covalent attachment of the (red) A14-DTPA-Gd-rhodamine imaging agent.

Work package leader(s): 
Peter Timmerman, Prof. dr.
Tilman Hackeng, Prof. dr.
12/12/2014