Figure 3.

IL-6 signaling is associated with reductions in NO bioavailability, due, in large part, to reductions in eNOS expression and activity as well as increases in NADPH oxidase-derived superoxide. This combination promotes oxidative stress, endothelial dysfunction as well as vascular hypertrophy and fibrosis. Many of the effects of angiotensin II, such as increased vascular superoxide, are enhanced by IL-6 mediated increases in AT1 receptor expression. Similarly, angiotensin II and IL-6 synergize to promote increases in fibroblast SMA-α, collagen, and MCP-1 (CCL2) expression which promote matrix expansion that ultimately contributes to increased arterial compliance and vascular stiffness. IL-6 also promotes immune cell infiltration of the vascular wall through increased expression of adhesion molecules, such as ICAM-1 and VCAM-1, and expression of MCP-1. IL-6, interleukin-6; eNOS, endothelial nitric oxide synthase; AT1R, angiotensin type 1 receptor; ICAM, intracellular adhesion molecule; VCAM, vascular cell adhesion molecule; MØ, macrophage; SMA, smooth muscle actin; MCP-1, monocyte chemoattractant protein-1.