Endothelial arginase II: A novel target for the treatment of atherosclerosis

Academic Article

Abstract

  • 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. © 2008 American Heart Association, Inc.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Ryoo S; Gupta G; Benjo A; Lim HK; Camara A; Sikka G; Lim HK; Sohi J; Santhanam L; Soucy K
  • Start Page

  • 923
  • End Page

  • 932
  • Volume

  • 102
  • Issue

  • 8