Graphical Abstract.
Myeloid cell-derived interleukin-6 (IL-6) overexpression was associated with systemic inflammation. Chronic myeloid cell-derived IL-6 evoked a significantly impaired endothelium-dependent aortic relaxation, increased aortic reactive oxygen species (ROS), and vascular dysfunction in resistance vessels. Vascular dysfunction was accompanied by a significant accumulation of myeloid cells in the aortic wall, an increased reactivity of myeloid cells, vascular fibrosis, and an altered vascular smooth muscle cell phenotype. This went in line with significantly elevated Mcp1, Cxcl1, and Rorc levels and an increased inducible NO synthase and endothelin-1 expression in LysM-IL-6OE aortas. Bone marrow (BM) transplantation studies revealed that vascular dysfunction and ROS formation were driven by BM cell-derived IL-6 in a dose-dependent manner.