FIG. 4.

Diverging roles of NADPH oxidase 4 in the vascular smooth muscle and endothelium. (A) In vascular smooth muscle cells, elevated glucose levels induce increased expression of Nox4, which promotes proliferation and macrophage infiltration, both crucial components of atherosclerotic progression. (B) In the endothelium, exposure to elevated glucose diminishes Nox4 expression leading to the loss of Nox4-mediated salutary homeostatic signaling, enhancing insulin signaling activation of Akt, vasorelaxation (directly by H₂O₂ and indirectly through SHP2 and eNOS), and potentially repression of Nox2 and MCP-1 expression. eNOS, endothelial nitric oxide synthase; SHP2, tyrosine-protein phosphatase nonreceptor type 11. Color images are available online.