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PMID: 22854495 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice.

Experimental & molecular medicine ·Vol. 44 ·No. 10 ·2012-10-31 ·Pages 594-602

Shin WS, Berkowitz DE, Ryoo SW

Abstract

The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.

MeSH Terms
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid/pharmacology Aging Animals Aorta/enzymology,physiopathology Arginase/genetics,metabolism Endothelium, Vascular/enzymology,physiopathology Enzyme Induction Gene Knockdown Techniques In Vitro Techniques Mice Mice, Inbred C57BL Nitric Oxide/metabolism Nitric Oxide Synthase Type III/metabolism RNA, Small Interfering/genetics Reactive Oxygen Species/metabolism Up-Regulation Vasoconstriction/drug effects
Chemicals
RNA, Small Interfering Reactive Oxygen Species Nitric Oxide 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid Nitric Oxide Synthase Type III Nos3 protein, mouse Arg1 protein, mouse Arg2 protein, mouse Arginase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Shin Woo Sung
Department of Biology College of Natural Sciences Kangwon National University Chuncheon 200-701, Korea.
Berkowitz Dan E
Ryoo Sung Woo
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Article Info
Journal
Experimental & molecular medicine
Abbr.
Exp Mol Med
ISSN
2092-6413
DOI
10.3858/emm.2012.44.10.068
Published
2012-10-31
Pages
594-602
Language
English
Region
United States
NLM ID
9607880
PMCID
PMC3490081
Subset
IM
External Links
PubMed source DOI: 10.3858/emm.2012.44.10.068 PMC Full Text View journal details
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