title: Arginase inhibition restores endothelial function in diet-induced obesity.
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.
authors: Department of Applied Bioscience, CHA University, Gyeonggi-do 463-836, Republic of Korea.
authors: Ji Hyung
authors: JH
authors: Chung
authors: Department of Food and Nutrition, Korea University, Seoul 136-704, Republic of Korea; Department of Public Health Sciences, Graduate School, Korea University, Seoul 136-703, Republic of Korea.
authors: Jiyoung
authors: J
authors: Moon
authors: Department of Food and Nutrition, Korea University, Seoul 136-704, Republic of Korea; Department of Public Health Sciences, Graduate School, Korea University, Seoul 136-703, Republic of Korea.
authors: Youn Sue
authors: YS
authors: Lee
authors: Severance Institute for Vascular and Metabolic Research, College of Medicine, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Hye-Kyung
authors: HK
authors: Chung
authors: Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Seung-Min
authors: SM
authors: Lee
authors: Department of Food and Nutrition, Korea University, Seoul 136-704, Republic of Korea; Department of Public Health Sciences, Graduate School, Korea University, Seoul 136-703, Republic of Korea; Korea University Guro Hospital, Korea University, Seoul 152-703, Republic of Korea. Electronic address: mjshin@korea.ac.kr.
authors: Min-Jeong
authors: MJ
authors: Shin
mesh_terms: D000818:Animals; D001119:Arginase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000502:physiology; D009573:Nitrites / Q000378:metabolism; D009765:Obesity / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D004791:Enzyme Inhibitors; C090509:Icam1 protein, mouse; C404735:N(omega)-hydroxynorarginine; D009573:Nitrites; D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1; D001120:Arginine; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C544448:Arg1 protein, mouse; C481673:Arg2 protein, mouse; D001119:Arginase
keywords: Arginase; Endothelial function; Nitric oxide; Obesity