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The article presents a study which aimed to determine whether oxidized low-density lipoprotein (OxLDL)-dependent activation of arginase causes impaired vascular nitric oxide (NO) production, increased ROS production, and endothelial dysfunction in atherogenic mice, and whether arginase inhibition prevents the development of endothelial dysfunction and vascular stiffness and attenuates plaque development in this model. The researchers noted that arginase activation appears to be responsible for the increased enzyme activity.

Oxidized low-density lipoproteins increase arginase activity and reciprocally decrease endothelial NO in human aortic endothelial cells. Here, we demonstrate that vascular endothelial arginase activity is increased in atherogenic-prone apolipoprotein E-null (ApoE(-/-)) and wild-type mice fed a high cholesterol diet. In ApoE(-/-) mice, selective arginase II inhibition or deletion of the arginase II gene (Arg II(-/-) mice) prevents high-cholesterol diet-dependent decreases in vascular NO production, decreases endothelial reactive oxygen species production, restores endothelial function, and prevents oxidized low-density lipoprotein-dependent increases in vascular stiffness. Furthermore, arginase inhibition significantly decreases plaque burden. These data indicate that arginase II plays a critical role in the pathophysiology of cholesterol-mediated endothelial dysfunction and represents a novel target for therapy in atherosclerosis.