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Atherosclerosis in apoE knockout mice infected with multiple pathogens
M S Burnett1, C A Gaydos, G E Madico
1Cardiovascular Research Institute, Washington Hospital Center, Washington, DC, USA.
Abstract:
Cytomegalovirus (CMV) and Chlamydia pneumoniae (CP) possibly contribute to atherosclerosis. Murine CMV (MCMV) and CP increase lesion size in apoE knockout mice. In this study, apoE knockout mice were infected with MCMV and CP to determine whether infection with multiple pathogens increases lesion size to a greater extent than either pathogen alone and whether infection with MCMV changes serum cytokine levels in a manner that could increase lesion development. One group of mice received MCMV at 2 weeks of age, followed by 2 doses of CP at 6 and 8 weeks of age. Additional groups received only MCMV or CP. Animals were killed at 16 weeks of age to determine lesion area. Infection with MCMV alone, CP alone, and both MCMV and CP increased lesion size 84% (P<.001), 70% (P<.0001), and 45% (P<.01), respectively. The MCMV-induced increase in circulating levels of interferon-gamma may have contributed to this increase.
Insights
Cytomegalovirus (CMV) and Chlamydia pneumoniae (CP) infection independently worsen atherosclerosis in mice. Co-infection with both pathogens showed a less pronounced increase in lesion size compared to single infections.
Area of Science:
- Cardiovascular Research
- Infectious Disease Immunology
- Atherosclerosis Pathogenesis
Background:
- Cytomegalovirus (CMV) and Chlamydia pneumoniae (CP) are suspected contributors to atherosclerosis development.
- Previous studies indicate that murine CMV (MCMV) and CP can exacerbate lesion size in apolipoprotein E knockout (apoE KO) mice.
Purpose of the Study:
- To investigate the combined effect of MCMV and CP infections on atherosclerosis lesion size in apoE KO mice.
- To determine if co-infection with MCMV and CP leads to a greater increase in lesion size than single-pathogen infections.
- To explore whether MCMV infection alters serum cytokine profiles in a way that promotes lesion development.
Main Methods:
- Apolipoprotein E knockout (apoE KO) mice were infected with MCMV at 2 weeks of age and CP at 6 and 8 weeks of age.
- Control groups received either MCMV alone or CP alone.
- Mice were euthanized at 16 weeks of age to quantify atherosclerotic lesion areas.
Main Results:
- MCMV infection alone increased lesion size by 84% (P<.001).
- CP infection alone increased lesion size by 70% (P<.0001).
- Co-infection with both MCMV and CP resulted in a 45% increase in lesion size (P<.01).
Conclusions:
- While both MCMV and CP individually promote atherosclerosis in apoE KO mice, their combined effect on lesion size was less than additive.
- Elevated circulating interferon-gamma levels following MCMV infection may contribute to increased lesion development.