Arginase inhibition restores endothelial function in diet-induced obesity

Ji Hyung Chung; Jiyoung Moon; Youn Sue Lee; Hye Kyung Chung; Seung Min Lee; Min Jeong Shin

doi:10.1016/j.bbrc.2014.07.083

Arginase inhibition restores endothelial function in diet-induced obesity

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

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

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 (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.

Original language	English
Pages (from-to)	179-183
Number of pages	5
Journal	Biochemical and biophysical research communications
Volume	451
Issue number	2
DOIs	https://doi.org/10.1016/j.bbrc.2014.07.083
Publication status	Published - 2014 Aug 22

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2013R1A1A2A10006101 ).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Arginase
Endothelial function
Nitric oxide
Obesity

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

Access to Document

10.1016/j.bbrc.2014.07.083

Cite this

@article{c83c77d18ebf4003af2a69559faefe16,

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 Nω-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.",

keywords = "Arginase, Endothelial function, Nitric oxide, Obesity",

author = "Chung, \{Ji Hyung\} and Jiyoung Moon and Lee, \{Youn Sue\} and Chung, \{Hye Kyung\} and Lee, \{Seung Min\} and Shin, \{Min Jeong\}",

note = "Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2013R1A1A2A10006101 ).",

year = "2014",

month = aug,

day = "22",

doi = "10.1016/j.bbrc.2014.07.083",

language = "English",

volume = "451",

pages = "179--183",

journal = "Biochemical and biophysical research communications",

issn = "0006-291X",

publisher = "Elsevier B.V.",

number = "2",

}

TY - JOUR

T1 - Arginase inhibition restores endothelial function in diet-induced obesity

AU - Chung, Ji Hyung

AU - Moon, Jiyoung

AU - Lee, Youn Sue

AU - Chung, Hye Kyung

AU - Lee, Seung Min

AU - Shin, Min Jeong

N1 - Funding Information: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( NRF-2013R1A1A2A10006101 ).

PY - 2014/8/22

Y1 - 2014/8/22

N2 - 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 Nω-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.

AB - 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 Nω-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.

KW - Arginase

KW - Endothelial function

KW - Nitric oxide

KW - Obesity

UR - https://www.scopus.com/pages/publications/84906934587

U2 - 10.1016/j.bbrc.2014.07.083

DO - 10.1016/j.bbrc.2014.07.083

M3 - Article

C2 - 25078625

AN - SCOPUS:84906934587

SN - 0006-291X

VL - 451

SP - 179

EP - 183

JO - Biochemical and biophysical research communications

JF - Biochemical and biophysical research communications

IS - 2

ER -

Arginase inhibition restores endothelial function in diet-induced obesity

Abstract

Bibliographical note

UN SDGs

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this