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A more recent version of this article appeared on December 1, 2007

Published online before print November 30, 2007
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Copyright © 2007 American Society for Investigative Pathology
American Journal of Pathology, doi:10.2353/ajpath.2007.060857


Accepted for publication August 24, 2007.


Article

Interleukin-4 Does Not Influence Development of Hypercholesterolemia or Angiotensin II-Induced Atherosclerotic Lesions in Mice

Victoria L. King*{dagger}@, Lisa A. Cassis*{dagger}, and Alan Daugherty*{dagger}

From the Cardiovascular Research Center,* and the Graduate Center for Nutritional Sciences,{dagger} University of Kentucky, Lexington, Kentucky

@ To whom correspondence should be addressed. E-mail: vicky.king{at}uky.edu.


   Abstract

Interleukin-4 (IL-4) has been detected in both human and mouse atherosclerotic lesions, although its effects on the development of the disease are undefined. We determined the role of IL-4 in the most commonly used murine models of atherosclerosis by defining the effects of exogenous delivery and genetic deficiency of this cytokine on both hypercholesterolemia and AngII-induced atherosclerosis in apolipoprotein E (apoE)-/- mice and different dietary stimuli in low-density lipoprotein (LDL) receptor-/- mice. Exogenous administration of IL-4 (1.1 ng g-1 day-1 i.p. for 30 days) into female apoE-/- mice had no effect on lesion size or composition in mice fed normal or saturated fat diets. Also, IL-4 deficiency had no significant effect on the size or composition of atherosclerotic lesions in two vascular areas of male and female apoE-/- mice fed either a normal or saturated fat diet. IL-4 deficiency was also studied in age-matched male mice infused with AngII (1000 ng kg-1 min-1) for 28 days. Whereas AngII infusion augmented atherosclerotic lesion formation, IL-4 deficiency did not influence atherosclerotic lesion size or composition. Finally, different dietary stimuli also had no effect on atherosclerotic lesion size in female LDL receptor-/- mice. These data demonstrate that IL-4 does not significantly influence the development of atherosclerotic lesions in apoE-/- mice of either gender or in female LDL receptor-/- mice, irrespective of the mode of induction of atherosclerosis.








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Copyright © 2007 by the American Society for Investigative Pathology.