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).
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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Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
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Contributors: |
Contribution | Contributors Name | Email | Pitt Username | ORCID  |
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Editor | Deli, Maria A. | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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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: |
22 Jun 2021 13:55 |
URI: |
http://d-scholarship.pitt.edu/id/eprint/13579 |
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