HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Papers In Press, published online ahead of print January 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800273-JLR200

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: M800273-JLR200v1 50/1/59    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moukdar, F. Articles by Collins, S. Search for Related Content PubMed PubMed Citation Articles by Moukdar, F. Articles by Collins, S. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol. 50, 59-70, January 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Reduced antioxidant capacity and diet-induced atherosclerosis in uncoupling protein-2-deficient mice

Fatiha Moukdar^1,*, Jacques Robidoux^2,*, Otis Lyght, Jingbo Pi^*, Kiefer W. Daniel^* and Sheila Collins^3,*,

^* The Endocrine Biology Program, Division of Translational Biology, The Hamner Institutes for Health Sciences, NC 27709
The Histopathology Core, The Hamner Institutes for Health Sciences, NC 27709
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27710
¹ Present address of F. Moukdar: Department of Physiology Brody School of Medicine, East Carolina University, Greenville, NC, 27834.
² Present address of J. Robidoux: Department of Pharmacology and Toxicology Brody School of Medicine, East Carolina University, Greenville, NC, 27834.

The online version of this article (available at http://www.jlr.org) contains supplementary data in the form of one figure.

Published, JLR Papers in Press, August 12, 2008.

This work was supported by a Research Award to SC from the American Diabetes Association.

³ To whom correspondence should be addressed. e-mail: scollins{at}thehamner.org or sheila.collins{at}duke.edu

Vascular dysfunction in response to reactive oxygen species (ROS) plays an important role in the development and progression of atherosclerotic lesions. In most cells, mitochondria are the major source of cellular ROS during aerobic respiration. Under most conditions the rates of ROS formation and elimination are balanced through mechanisms that sense relative ROS levels. However, a chronic imbalance in redox homeostasis is believed to contribute to various chronic diseases, including atherosclerosis. Uncoupling protein-2 (UCP2) is a mitochondrial inner membrane protein shown to be a negative regulator of macrophage ROS production. In response to a cholesterol-containing atherogenic diet, C57BL/6J mice significantly increased expression of UCP2 in the aorta, while mice lacking UCP2, in the absence of any other genetic modification, displayed significant endothelial dysfunction following the atherogenic diet. Compared with wild-type mice, Ucp2^–/– mice had decreased endothelial nitric oxide synthase, an increase in vascular cell adhesion molecule-1 expression, increased ROS production, and an impaired ability to increase total antioxidant capacity. These changes in Ucp2^–/– mice were associated with increased aortic macrophage infiltration and more numerous and larger atherosclerotic lesions. These data establish that in the vasculature UCP2 functions as an adaptive antioxidant defense to protect against the development of atherosclerosis in response to a fat and cholesterol diet.

Supplementary key words UCP2 • reactive oxygen species • ROS • inflammation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Pi, Y. Bai, K. W. Daniel, D. Liu, O. Lyght, D. Edelstein, M. Brownlee, B. E. Corkey, and S. Collins Persistent Oxidative Stress Due to Absence of Uncoupling Protein 2 Associated with Impaired Pancreatic {beta}-Cell Function Endocrinology, July 1, 2009; 150(7): 3040 - 3048. [Abstract] [Full Text] [PDF]