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Arginase activities and global arginine bioavailability in wild-type and ApoE-deficient mice: Responses to high fat and high cholesterol diets

Erdely, A and Kepka-Lenhart, D and Salmen-Muniz, R and Chapman, R and Hulderman, T and Kashon, M and Simeonova, PP and Morris, SM (2010) Arginase activities and global arginine bioavailability in wild-type and ApoE-deficient mice: Responses to high fat and high cholesterol diets. PLoS ONE, 5 (12).

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Abstract

Increased catabolism of arginine by arginase is increasingly viewed as an important pathophysiological factor in cardiovascular disease, including atherosclerosis induced by high cholesterol diets. Whereas previous studies have focused primarily on effects of high cholesterol diets on arginase expression and arginine metabolism in specific blood vessels, there is no information regarding the impact of lipid diets on arginase activity or arginine bioavailability at a systemic level. We, therefore, evaluated the effects of high fat (HF) and high fat-high cholesterol (HC) diets on arginase activity in plasma and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE-/- and wild-type C57BL/6J mice. HC and HF diets led to reduced global arginine bioavailability in both strains. The HC diet resulted in significantly elevated plasma arginase in both strains, but the HF diet increased plasma arginase only in apoE-/- mice. Elevated plasma arginase activity correlated closely with increased alanine aminotransferase levels, indicating that liver damage was primarily responsible for elevated plasma arginase. The HC diet, which promotes atherogenesis, also resulted in increased arginase activity and expression of the type II isozyme of arginase in multiple tissues of apoE-/- mice only. These results raise the possibility that systemic changes in arginase activity and global arginine bioavailability may be contributing factors in the initiation and/or progression of cardiovascular disease.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Erdely, A
Kepka-Lenhart, D
Salmen-Muniz, R
Chapman, R
Hulderman, T
Kashon, M
Simeonova, PP
Morris, SMsmorris@pitt.eduSMORRIS0000-0002-8614-9679
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorDeli, Maria A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 20 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0015253
Refereed: Yes
MeSH Headings: Alanine Transaminase--metabolism; Animal Feed; Animals; Apolipoproteins E--genetics; Arginase--blood; Arginase--metabolism; Arginine--pharmacology; Biological Availability; Cholesterol--metabolism; Citrulline--genetics; Diet; Isoenzymes--chemistry; Male; Mice; Mice, Inbred C57BL; Ornithine--genetics; Reverse Transcriptase Polymerase Chain Reaction
Other ID: NLM PMC2997799
PubMed Central ID: PMC2997799
PubMed ID: 21151916
Date Deposited: 22 Aug 2012 21:51
Last Modified: 02 Feb 2019 16:57
URI: http://d-scholarship.pitt.edu/id/eprint/13579

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