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Mechanisms involved on CCN2(IV) responses in VSMCs. CCN2(IV) binds to EGFR and activates Nox1 leading to O2•− production. CCN2(IV) through this signaling mechanism increases protein nitrosylation and endothelial dysfunction. In addition, O2•−, acting as a second messenger, activates the NF-κB pathway and induces its related proinflammatory genes.
