Arginase inhibition restores endothelial function in diet-induced obesity

Biochem Biophys Res Commun. 2014 Aug 22;451(2):179-83. doi: 10.1016/j.bbrc.2014.07.083. Epub 2014 Jul 29.

Abstract

Arginase may play a major role in the regulation of vascular function in various cardiovascular disorders by impairing nitric oxide (NO) production. In the current study, we investigated whether supplementation of the arginase inhibitor N(ω)-hydroxy-nor-l-arginine (nor-NOHA) could restore endothelial function in an animal model of diet-induced obesity. Arginase 1 expression was significantly lower in the aorta of C57BL/6J mice fed a high-fat diet (HFD) supplemented with nor-NOHA (40mgkg(-1)/day) than in mice fed HFD without nor-NOHA. Arginase inhibition led to considerable increases in eNOS expression and NO levels and significant decreases in the levels of circulating ICAM-1. These findings were further confirmed by the results of siRNA-mediated knockdown of Arg in human umbilical vein endothelial cells. In conclusion, arginase inhibition can help restore dysregulated endothelial function by increasing the eNOS-dependent NO production in the endothelium, indicating that arginase could be a therapeutic target for correcting obesity-induced vascular endothelial dysfunction.

Keywords: Arginase; Endothelial function; Nitric oxide; Obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginase / antagonists & inhibitors*
  • Arginase / genetics
  • Arginase / physiology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Diet, High-Fat / adverse effects
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / enzymology*
  • Endothelium, Vascular / physiopathology*
  • Enzyme Inhibitors / pharmacology
  • Gene Expression
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / physiology
  • Nitrites / metabolism
  • Obesity / enzymology*
  • Obesity / etiology
  • Obesity / physiopathology*
  • RNA, Small Interfering / genetics

Substances

  • Enzyme Inhibitors
  • Icam1 protein, mouse
  • N(omega)-hydroxynorarginine
  • Nitrites
  • RNA, Small Interfering
  • Intercellular Adhesion Molecule-1
  • Arginine
  • Nitric Oxide Synthase Type III
  • Nos3 protein, mouse
  • Arg1 protein, mouse
  • Arg2 protein, mouse
  • Arginase