Highlights
- •Genital Chlamydia infection exacerbated atherosclerosis in two independent hyperlipidemic mouse models of atherosclerosis.
- •Chlamydia infection increased pro-inflammatory cytokines, chemokines, and VCAM-1 expression.
- •Interestingly, Chlamydia infection showed uterine pathology only in apoE-deficient mice.
Abstract
Background and aims
Atherosclerosis is a chronic inflammatory disease, and recent studies have shown that
infection at remote sites can contribute to the progression of atherosclerosis in
hyperlipidemic mouse models. In this report, we tested the hypothesis that genital
Chlamydia infection could accelerate the onset and progression of atherosclerosis.
Methods
Apolipoprotein E (Apoe−/−) and LDL receptor knockout (Ldlr−/−) mice on a high-fat diet were infected intra-vaginally with Chlamydia muridarum. Atherosclerotic lesions on the aortic sinuses and in the descending aorta were assessed
at 8-weeks post-infection. Systemic, macrophage, and vascular site inflammatory responses
were assessed and quantified.
Results
Compared to the uninfected groups, infected Apoe−/− and Ldlr−/− mice developed significantly more atherosclerotic lesions in the aortic sinus and
in the descending aorta. Increased lesions were associated with higher circulating
levels of serum amyloid A-1, IL-1β, TNF-α, and increased VCAM-1 expression in the
aortic sinus, suggesting an association with inflammatory responses observed during
C. muridarum infection. Genital infection courses were similar in Apoe−/−, Ldlr−/−, and wild type mice. Further, Apoe−/− mice developed severe uterine pathology with increased dilatations. Apoe-deficiency
also augmented cytokine/chemokine response in C. muridarum infected macrophages, suggesting that the difference in macrophage response could
have contributed to the genital pathology in Apoe−/− mice.
Conclusions
Overall, these studies demonstrate that genital Chlamydia infection exacerbates atherosclerotic lesions in hyperlipidemic mouse and suggest
a novel role for Apoe in full recovery of uterine anatomy after chlamydial infection.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: September 27, 2019
Accepted:
September 26,
2019
Received in revised form:
September 11,
2019
Received:
March 20,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
