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Research carried out by the recipents of the Young Investigator Grants (YIG)

One key mission of the Cardiovascular Program at KI is to support young and promising researchers in the cardiovascular field, preferably recruited from international top universities other than KI. To achieve this goal, CVP has announced Young Investigator Grants (YIG). All candidates are evaluated by three external referees.

 

DANIEL KETELHUTH

CARDIOVASCULAR IMMUNOLOGY AND METABOLISM RESEARCH GROUP

Heart disease and stroke, largely due to atherosclerosis and atherothrombosis, are the major causes of death in the western world and increasingly so in developing countries.

Atherosclerosis is a chronic inflammatory disease in which lipids accumulate, eliciting an inflammatory response in the arterial wall. Atherothrombosis, defined as disruption of the atherosclerotic plaque and superimposed thrombosis, accounts for most of the lethal consequences of atherosclerosis. These life-threatening complications of atherosclerotic cardiovascular diseases (CVD) are linked primarily to an acute complication that is caused by prothrombotic changes in the plaque, including weakening of the fibrous cap, plaque disruption, and exposure of the core’s procoagulant material to coagulation proteins and platelets in the blood.

The aim of our research is to develop new therapeutic approaches for the prevention and treatment of atherosclerotic CVDs. An important aspect of our projects is to identify new drug candidates that can 1) influence blood lipid levels, 2) reduce ongoing inflammation in the vessel wall, 3) promote plaque stabilization, and 4) decrease risk of thrombosis.

Our recent work revealed that the Kynurenine pathway of tryptophan degradation, which lays downstream of Indoleamine 2,3-dioxygenase (IDO), is a very attractive target for the development of novel therapies. Our current projects aim at investigating the mechanisms by which the Kynurenine pathway of tryptophan degradation regulates lipid metabolism, macrophage and smooth muscle cell responses, and platelet activation—all events that can influence plaque formation, stabilization, rupture, and thrombus formation.



Representative samples from dissected aortic arches from hyperlipidemic mice receiving anti-atherosclerotic treatment or untreated controls. Accumulated lipids in the atherosclerotic plaques are stained in red by Sudan IV.

 

Artery wall of a hyperlipidemic mouse. Immunofluorescence staining of atherosclerotic plaque (also known as atheroma) shows cellular infiltration (blue) and building up fibrous cap (yellow). VCAM-1 staining (red) shows signs of increased inflammation in the vessel wall.