Infectious Agents Are Not Necessary for Murine Atherogenesis

doi:10.1084/jem.191.8.1437

Published online 18 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

Correspondence to: Samuel D. Wright, Merck Research Laboratories, Lipid Biochemistry, P.O. Box 2000, RY80W-250, 126 E. Lincoln Ave., Rahway, NJ 07065. Tel:732-594-3086 Fax:732-594-1169 E-mail: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 with animals incapableof responding to bacterial lipopolysaccharide. Atherogenesiswas unaffected in doubly deficient animals. We further testedthe role of infectious agents by creating a colony of germ-freeapo E^-/- mice. These animals are free of all microbial agents(bacterial, viral, and fungal). Atherosclerosis in germ-freeanimals was not measurably different from that in animals raisedwith ambient levels of microbial challenge. These studies showthat infection is not necessary for murine atherosclerosis andthat, unlike peptic ulcer, Koch's postulates cannot be fulfilledfor any infectious agent in atherosclerosis.

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

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