Phosphorylation of Smooth Muscle 22α Facilitates Angiotensin II–Induced ROS Production Via Activation of the PKCδ-P47phox Axis Through Release of PKCδ and Actin Dynamics and Is Associated With Hypertrophy and Hyperplasia of Vascular Smooth Muscle Cells In Vitro and In Vivo

Rationale:We have demonstrated that smooth muscle (SM) 22α inhibits cell proliferation via blocking Ras-ERK1/2 signaling in vascular smooth muscle cells (VSMCs) and in injured arteries. The recent study indicates that SM22α disruption can independently promote arterial inflammation through activation of reactive oxygen species (ROS)-mediated NF-κB pathways. However, the mechanisms by which SM22α controls ROS production have not been characterized. Objective:To investigate how SM22α disruption promotes ROS production and to characterize the underlying mechanisms. Methods and Results:ROS level was measured by dihydroethidium staining for superoxide and TBA assay for malondialdehyde, respectively. We showed that downregulation and phosphorylation of SM22α were associated with angiotensin (Ang) II–induced increase in ROS production in VSMCs of rats and human. Ang II induced the phosphorylation of SM22α at Serine 181 in an Ang II type 1 receptor–PKCδ pathway–dependent manner. Phosphorylated SM22α activated the...