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Selective endothelial overexpression of arginase ii induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice

Vaisman, BL and Andrews, KL and Khong, SML and Wood, KC and Moore, XL and Fu, Y and Kepka-Lenhart, DM and Morris, SM and Remaley, AT and Chin-Dusting, JPF (2012) Selective endothelial overexpression of arginase ii induces endothelial dysfunction and hypertension and enhances atherosclerosis in mice. PLoS ONE, 7 (7).

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Abstract

Background: Cardiovascular disorders associated with endothelial dysfunction, such as atherosclerosis, have decreased nitric oxide (NO) bioavailability. Arginase in the vasculature can compete with eNOS for L-arginine and has been implicated in atherosclerosis. The aim of this study was to evaluate the effect of endothelial-specific elevation of arginase II expression on endothelial function and the development of atherosclerosis. Methodology/Principal Findings: Transgenic mice on a C57BL/6 background with endothelial-specific overexpression of human arginase II (hArgII) gene under the control of the Tie2 promoter were produced. The hArgII mice had elevated tissue arginase activity except in liver and in resident peritoneal macrophages, confirming endothelial specificity of the transgene. Using small-vessel myography, aorta from these mice exhibited endothelial dysfunction when compared to their non-transgenic littermate controls. The blood pressure of the hArgII mice was 17% higher than their littermate controls and, when crossed with apoE -/- mice, hArgII mice had increased aortic atherosclerotic lesions. Conclusion: We conclude that overexpression of arginase II in the endothelium is detrimental to the cardiovascular system.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Vaisman, BL
Andrews, KL
Khong, SML
Wood, KC
Moore, XL
Fu, Y
Kepka-Lenhart, DM
Morris, SMsmorris@pitt.eduSMORRIS0000-0002-8614-9679
Remaley, AT
Chin-Dusting, JPF
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorBearden, Shawn EUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 19 July 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 7
DOI or Unique Handle: 10.1371/journal.pone.0039487
Schools and Programs: School of Medicine > Microbiology and Molecular Genetics
Refereed: Yes
Other ID: NLM PMC3400622
PubMed Central ID: PMC3400622
PubMed ID: 22829869
Date Deposited: 03 Aug 2012 16:00
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/13243

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