CASyM winter school of Systems Medicine took place between March 29th and April 1st 2017 in Ljubljana, Slovenia and is entitled »The 3rd SysBioMed hands-on tutorial: Systems Medicine Approaches in Personalized Medicine«
Role of endothelial IkB kinase 2 in atherosclerosis
Marion Mussbacher1, Manuel Salzmann1, José Basílio1, Mario Kuttke2, Hans Volek1, Bastian Hösel1, Ulrike Resch1, Alice Assinger2, Johannes Schmid1
1Institute for Vascular Biology and Thrombosis Research, Medical University of Vienna, Vienna, Austria, 2Institute of Physiology, Medical University Of Vienna, Vienna, Austria
Aim The transcription factor NF-κB has a key role in inflammation and is also an important regulator of genes involved in coagulation and thrombosis. NF-κB is activated by a number of signaling pathways that converge, in the majority of cases, at the level of IκB kinase 2 (IKK2). Our study uses constitutive active IKK2 (caIKK2) in a conditional transgene mouse model to mimic chronic inflammation specifically in endothelial cells and to test a potential aggravating impact on the onset of atherosclerosis. Results Mice bearing inducible, aortic-EC-specific Cre recombinase on an ApoE-deficient background were crossed with a strain expressing caIKK2 downstream of a loxP-flanked stop cassette and fed with cholesterol-rich high fat diet for 12 weeks. RNA sequencing analysis of the aortic transcriptome was done 10 days after induction, before starting the high fat diet and revealed activation of inflammatory networks (involving TNF, IFNγ and IL1β), which were accompanied by increased immune cell infiltration. Flow cytometric analysis of lymph nodes and spleen tissue was used to detect infiltration and activation of B and T cells. Conclusion In summary, we conclude that endothelial NF-κB signaling orchestrates immune cell responses within the arterial wall and therefore plays an important role in the pathogenesis of atherosclerosis. Furthermore, our data indicate that inflammatory endothelial cell activation causes an early B cell and T cell responses in the pathogenesis of atherosclerosis before the occurrence of cholesterol-rich lesions.
2006 - University of Ljubljana, Faculty of Medicine, Center for Functional Genomics and Bio-chips.