DCATHEROAZMVZ - Dendritic Cells in the Pathogenesis of Atherosclerosis 

Time period:
2007-01-01 - 2008-12-31
Marie Curie Actions (MCA)

Atherosclerosis is the main cause of death in the industrial world. The understanding of the pathogenesis has led to the notion of atherosclerosis as a chronic inflammatory disease. The evidence of a network of vascular-associated dendritic cells (DC) in arteries of healthy young individuals as well as findings demonstrating an infiltration of atherosclerotic plaques, where DC can accumulation in close contact with macrophages/ monocytes and T-cells implies an important role of DC suggests a functional role of DC in the activation of the vascular immune system and in the pathogenesis of atherosclerosis. So far the molecular mechanisms regulating the recruitment and causative role of DC in the formation of atherosclerotic plaques remains to be elucidated. DC derive from hematopoietic cells but also peripheral monocytes. So far, several different markers have been used to detect DC in atherosclerotic lesions, however, these are of low specificity. The CCL17 chemokine (also referred to as dendrokine) is expressed only by mature DC. Using an eGFP knock-in, CCL17 knock-out, crossed into the atherosclerosis prone apolipoprotein E deficient (apoE-/-) background, will allow us to specifically study the role of DC in pathological pathways operative in atherosclerosis. The infiltration and localizatinon of DC in atherosclerotic lesions will be studied by detection of GFP-expressing DC in heterozygous CCL17E/+ apoE-/- mice by dual photon microscopy. Double knockout mice will be used to evaluate the role of DC and of their effector chemokines CCL17 in lesion development in native atherosclerosis. Furthermore, in vitro and in vivo assays will be performed to investigate the instruction or modulation of a specific immune response during the initiation and progression of atherosclerotic lesions.

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Last updated on 2011-08-18 at 19:12