Endothelial dysfunction after repeated Chlamydia pneumoniae infection in apolipoprotein E-knockout mice

Area of Science:

• Cardiovascular Research
• Infectious Disease Immunology
• Vascular Biology

Background:

• Endothelial nitric oxide (NO) regulates arterial relaxation; diminished NO activity is linked to early atherosclerosis.
• Chlamydia pneumoniae infection is a potential factor in cardiovascular disease development.

Purpose of the Study:

• To investigate the impact of Chlamydia pneumoniae inoculation on endothelium-dependent aortic relaxation in apolipoprotein E-knockout (apoE-KO) mice.

Main Methods:

• ApoE-KO mice were exposed to repeated intranasal Chlamydia pneumoniae or saline inoculations over six weeks.
• Aortic rings were isolated and relaxation responses to methacholine were measured in vitro.
• The roles of the nitric oxide (NO) pathway and cyclooxygenase (COX) pathway were assessed using L-NAME and diclofenac.

Main Results:

• Chlamydia pneumoniae infection significantly attenuated endothelium-dependent relaxation in aortic rings at six weeks post-inoculation.
• The impaired relaxation was observed both in the absence and presence of L-NAME, indicating NO pathway involvement.
• Diclofenac enhanced relaxation in infected mice pretreated with L-NAME at two weeks, suggesting a role for cyclooxygenase products.

Conclusions:

• Chlamydia pneumoniae infection impairs arterial endothelial function, with the NO pathway being a primary mediator.
• Cyclooxygenase-dependent vasoconstricting products may also contribute to infection-induced impaired relaxation.
• These findings support the hypothesis that Chlamydia pneumoniae infection plays a role in the pathogenesis of atherosclerosis.