Arginase II: Atherogenesis Beyond Enzyme Activity

I t is now well established that endothelial cells (EC) andvascular smooth muscle cells (VSMC) are two specialized and interacting components of the vascular wall that orches-trate the pathogenesis of atherosclerosis through complex signaling cascades. Endothelial dysfunction is an early and critical event that initiates atherogenesis. This is mostly mediated through impaired regulation of endothelial nitric oxide synthase (eNOS) with a resultant decrease in vasopro-tective nitric oxide (NO) and increased reactive oxygen species (ROS) production that promotes vascular injury. Emerging data support upregulation of Arginase II (ArgII) in the pathobiology of atherogenesis, and most investigations have focused on deleterious effects of ArgII in EC, where it competes with eNOS for the common substrate L-arginine. Depletion of L-arginine by elevated ArgII activity reciprocally regulates eNOS and results in increased production of harmful oxidants and decreased NO availability. Apoptosis and senescence of VSMC promote plaque rupture in late-stage atherosclerotic vessels.1 The mechanisms involved in this process are still unclear and are under active investigation. In an interesting article in this issue of JAHA entitle