Chronic inflammation is the underlying cause of many diseases, including cardiovascular, metabolic, and neurological conditions,
amongst others. Modulation of the inflammatory response has the potential to reduce disease severity. In order to develop
novel therapeutic targets for chronic inflammatory diseases, detailed knowledge about the complex pathophysiological mechanisms
underlying these diseases is required. Therefore we aimed to elucidate the role of hematopoietic stem and progenitor cells
(HSPCs) in atherosclerosis. In addition, we analyzed the role of CD40L-CD40-TRAF interactions in the development of inflammatory
diseases. We conclude that the results described in this thesis identify novel pathophysiological mechanisms at the level
of HSPCs that promotes the development of atherosclerosis. Elucidation of the molecular mechanism may result in the identification
of novel therapeutic targets for these conditions. Additionally, we demonstrate that platelet CD40 and CD40L aggravate atherosclerosis.
Finally, we show that CD40-TRAF6 interactions promote atherosclerosis and obesity and we identify small molecule-mediated
inhibition of the CD40-TRAF6 interaction as a promising therapeutic strategy for atherosclerosis, obesity and its complications,
and multiple sclerosis.
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