Immunopathogenic mechanisms in coronary artery disease

Despite state of the art cardiovascular treatment, coronary artery disease (CAD) with development of acute coronary syndromes are still common manifestations of atherosclerosis, suggesting that important pathogenic mechanisms remain active and unmodified by the present treatment modalities. Based on several studies, including our own original observations, we hypothesize that T cell activation could represent such unmodified mechanisms, playing an important pathogenic role in CAD by enhancing atherogenesi s and by promoting plaque rupture with subsequent development of acute coronary syndromes. In the current project this hypothesis will be investigated by different clinical and experimental approaches particularly focusing on: (i) The pathogenic role of r egulatory T cells. (ii) The pathogenic role of homeostatic chemokines (i.e., CCL19 and CCL21 and their common receptor CCR7). (iii). Therapeutic intervention targeting T cell activation in acute coronary syndromes as a proof of concept study. The current project attempts to study inflammatory and immunologic mechanisms in CAD. The project deals with unresolved issues in the intersection between cardiology, immunology and molecular biology. The studies represent a unique opportunity to establish a bridge b etween bench and bedside, which is of the utmost importance in order to exploit in clinical medicine the recent development in immunology and molecular biology. The project will focus on new pathogenic mechanisms in CAD with the ambitions to delineate nov el therapeutic targets possibly leading to new treatment modalities in this disorder. With respect to the important health problem this disorder represents both in Norway and in other countries, such new therapeutic options may have important consequences . The current project will also be relevant for other disorders in which T cell activation is involved as an important pathogenic factor such as autoimmune and some chronic infectious disorders.