Infectious agents are not necessary for murine atherogenesis

Recent work has revealed correlations between bacterial or viral infections and atherosclerotic disease. One particular bacterium, Chlamydia pneumonia e, has been observed at high frequency in human atherosclerotic lesions, pr ompting the hypothesis that infectious agents may be necessary for the init iation or progression of atherosclerosis. To determine if responses to gram -negative bacteria are necessary for atherogenesis, we first bred atheroscl erosis-prone apolipoprotein (apo) E-/- (deficient) mice with animals incapa ble of responding to bacterial lipopolysaccharide. Atherogenesis was unaffe cted in doubly deficient animals. We further tested the role of infectious agents by creating a colony of germ-free apo E-/- mice. These animals are f ree of all microbial agents (bacterial, viral, and fungal). Atherosclerosis in germ-free animals was not measurably different from that in animals rai sed with ambient levels of microbial challenge. These studies show that inf ection is not necessary for murine atherosclerosis and that, unlike peptic ulcer, Koch's postulates cannot be fulfilled for any infectious agent in at herosclerosis.