Infectious Agents Are Not Necessary for Murine Atherogenesis

doi:10.1084/jem.191.8.1437

Published online 17 April 2000.

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© The Rockefeller University Press, 0022-1007/2000/4/1437/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 8, April 17, 2000 1437-1442

Brief Definitive Report

Infectious Agents Are Not Necessary for Murine Atherogenesis

Samuel D. Wright^a, Charlotte Burton^a, Melba Hernandez^a, Heide Hassing^a, Judy Montenegro^a, Steve Mundt^a, Sushma Patel^a, Deborah J. Card^a, Anne Hermanowski-Vosatka^a, James D. Bergstrom^a, Carl P. Sparrow^a, Patricia A. Detmers^a, and Yu-Sheng Chao^a

^a Department of Lipid Biochemsitry, Merck Research Laboratories, Rahway, New Jersey 07065
Merck Research Laboratories, Lipid Biochemistry, P.O. Box 2000, RY80W-250, 126 E. Lincoln Ave., Rahway, NJ 07065.732-594-1169732-594-3086

samuel_wright{at}merck.com

Recent work has revealed correlations between bacterial or viralinfections and atherosclerotic disease. One particular bacterium,Chlamydia pneumoniae, has been observed at high frequency inhuman atherosclerotic lesions, prompting the hypothesis thatinfectious agents may be necessary for the initiation or progressionof atherosclerosis. To determine if responses to gram-negativebacteria are necessary for atherogenesis, we first bred atherosclerosis-proneapolipoprotein (apo) E^–/– (deficient) mice withanimals incapable of responding to bacterial lipopolysaccharide.Atherogenesis was unaffected in doubly deficient animals. Wefurther tested the role of infectious agents by creating a colonyof germ-free apo E^–/– mice. These animals are freeof all microbial agents (bacterial, viral, and fungal). Atherosclerosisin germ-free animals was not measurably different from thatin animals raised with ambient levels of microbial challenge.These studies show that infection is not necessary for murineatherosclerosis and that, unlike peptic ulcer, Koch's postulatescannot be fulfilled for any infectious agent in atherosclerosis.

Key Words: atherosclerosis • apolipoprotein E knockout • germ-free animal • Toll • cholesterol

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