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 pneumoniae, has been observed at high frequency in human atherosclerotic lesions, prompting the hypothesis that infectious agents may be necessary for the initiation or progression of atherosclerosis. To determine if responses to gram-negative bacteria are necessary for atherogenesis, we first bred atherosclerosis-prone apolipoprotein (apo) E−/− (deficient) mice with animals incapable of responding to bacterial lipopolysaccharide. Atherogenesis was unaffected 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 free of all microbial agents (bacterial, viral, and fungal). Atherosclerosis in germ-free animals was not measurably different from that in animals raised with ambient levels of microbial challenge. These studies show that infection is not necessary for murine atherosclerosis and that, unlike peptic ulcer, Koch's postulates cannot be fulfilled for any infectious agent in atherosclerosis.

• Publication year

  2000

• Venue

  Journal of Experimental Medicine

• Publication date

  2000-04-17

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.191.8.1437PMID 10770809PMCID 2193142
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Chlamydia pneumoniae infection accelerates the progression of atherosclerosis in apolipoprotein E-deficient mice.

  1999cited by this paper
• Does Chlamydia pneumoniae cause atherosclerosis?

  1999cited by this paper
• Toll, A New Piece in the Puzzle of Innate Immunity

  1999cited by this paper
• Lack of association between seropositivity to Chlamydia pneumoniae and carotid atherosclerosis.

  1999cited by this paper
• Randomized secondary prevention trial of azithromycin in patients with coronary artery disease and serological evidence for Chlamydia pneumoniae infection: The Azithromycin in Coronary Artery Disease: Elimination of Myocardial Infection with Chlamydia (ACADEMIC) study.

  1999cited by this paper
• Atherosclerosis--an inflammatory disease.

  1999cited by this paper
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  1999cited by this paper
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  1999cited by this paper
• Evidence of systemic dissemination of Chlamydia pneumoniae via macrophages in the mouse.

  1998cited by this paper
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  1998cited by this paper
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  1998cited by this paper
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  1998cited by this paper
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  1998cited by this paper
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  1998cited by this paper
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  1998cited by this paper
• Chlamydia pneumoniae and cardiovascular disease.

  1998cited by this paper
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  1998cited by this paper
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  1997cited by this paper
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  1997cited by this paper
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  1996cited by this paper
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  1996cited by this paper
• Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E.

  1995cited by this paper
• Chlamydia pneumoniae (TWAR) in coronary arteries of young adults (15-34 years old).

  1995cited by this paper
• Helicobacter pylori in peptic ulcer disease.

  1995cited by this paper
• Detection of Chlamydia pneumoniae TWAR in human coronary atherectomy tissues.

  1995cited by this paper
• Association of Helicobacter pylori and Chlamydia pneumoniae infections with coronary heart disease and cardiovascular risk factors

  1995cited by this paper
• ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.

  1994cited by this paper
• NIH Consensus Conference. Helicobacter pylori in peptic ulcer disease. NIH Consensus Development Panel on Helicobacter pylori in Peptic Ulcer Disease.

  1994cited by this paper
• Helicobacter pylori in peptic ulcer disease.

  1994cited by this paper
• Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells.

  1992cited by this paper
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  1992cited by this paper
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  1992cited by this paper
• The epidemiology of Helicobacter pylori infection.

  1991cited by this paper
• The germ-free animal in biomedical research.

  1984cited by this paper
• Herpesvirus-induced atherosclerosis in chickens.

  1983cited by this paper
• The picomole determination of free and total cholesterol in cells in culture.

  1978cited by this paper
• Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells.

  1978cited by this paper
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  1957cited by this paper

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