Figure 12.

Schematic showing putative interactions between lipid rafts/caveolae, Nox isoforms, DJ-1 and vascular signaling in conditions where lipid rafts/caveolae are intact and when they are discrupted. (i) When cholesterol-rich microdomains are intact, likely in physiological conditions, Nox1 and Nox5 are regulated and ROS production is controlled. Nox4 which is constitutively active, localizes in the cytoplasm where it generates mainly H₂O₂, which may be vasoprotective. (ii) During lipid-raft disruption, which may occur in pathological conditions or when the Ang II system is upregulated, Nox1 and Nox5 are activated leading to excessive ROS production and oxidative stress. This promotes increased redox-dependent signaling through multiple downstream pathways that influence VSMC function. P phosphorylation, Ox oxidation, MLC20 myosin light chain, ERM Ezrin–Radixin–Moesin.