Ulrike Giese
Vadim Tchaikovski

Kooperationspartner:
Andreas Gardemann, Inst. Klin. Chemie und Pathobiochemie; Michael Naumann, Inst. f. Experimentelle Innere Medizin

Atherosclerosis is widely appreciated as a local inflammatory disease of the vascular wall. Its development and progression are critically dependent on NF-kB-dependent gene products. Recently, it became evident that plaque progression is to a large part due to defective termination of local inflammation. This highly ordered process, called inflammation resolution, is actively orchestrated by distinct cellular events and endogenous chemical mediators. Among these, lipid mediators which are derivatives of ω-3 poly-unsaturated fatty acids (PUFAs) have emerged as a novel genus of potent and stereoselective players that counter-regulate chronic inflammation and stimulate molecular and cellular events that define resolution. NF-kB system plays a central role in the progression of atherosclerotic plaques, promoting an un-controlled cell apoptosis, sustaining a pro-inflammatory cell phenotype and therefore leading to plaque instability. However, there is still a substantial lack of knowledge how these novel pro-resolving mediators influence NF-kB signaling. This project aims to investigate how pro-resolving lipid mediators modulate (1.) the classical canonical NF-kB signaling and (2.) the stress-activated NF-kB system; (3.) Furthermore, their effect on macrophage phenotype and behavior will be elucidated.