Arginase inhibition restores endothelial function in diet-induced obesity

作者：Chung Ji Hyung; Moon Jiyoung; Lee Youn Sue; Chung Hye Kyung; Lee Seung Min; Shin Min Jeong^*

来源：Biochemical and Biophysical Research Communications, 2014, 451(2): 179-183.

DOI：10.1016/j.bbrc.2014.07.083

• Arginase
• Endothelial function
• Nitric oxide
• Obesity

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-omega-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 (40 mg kg(-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.

• 出版日期2014-8-22