Cardiovascular changes after pneumonia in a dual disease mouse model
Benjamin Bartlett1,2, Herbert P Ludewick1, Shipra Verma3,4
1Department of Advanced Clinical and Translational Cardiovascular Imaging, Harry Perkins Institute of Medical Research, Murdoch, Australia.
Abstract:
Residual inflammation in cardiovascular organs is thought to be one of the catalysts for the increased risk of cardiovascular complications seen following pneumonia. To test this hypothesis, we investigated changes in plaque characteristics and inflammatory features in ApoE-/- mouse aorta and heart following pneumonia. Male ApoE-/- mice were fed a high fat diet for 8 weeks before intranasal inoculation with either Streptococcus pneumoniae serotype 4 (test group) or phosphate buffered saline (control group). Mice were sacrificed at 2-, 7- and 28-days post-challenge. Changes in plaque burden and characteristics in aortic root and thoracic aorta were characterized by Oil red O and Trichrome stains. Inflammatory changes were investigated by FDG-PET imaging and immunofluorescence staining. We found TIGR4-infected mice present with increased plaque presence in the aortic root and thoracic aorta at 2- and 28-days post-inoculation, respectively. Aortic wall remodelling was also more pronounced in mice challenged with pneumococci at 28 days post-inoculation. Aortic root plaques of infected mice had reduced collagen and smooth muscle cells, consistent with an unstable plaque phenotype. Pneumonia alters plaque burden, plaque characteristics, and aortic wall remodelling in ApoE-/- mice. These effects caused by Streptococcus pneumoniae TIGR4, may contribute to the increased risk of cardiovascular complications seen in survivors of this infection.
Insights
Pneumonia caused by Streptococcus pneumoniae TIGR4 increases cardiovascular disease risk by altering aorta plaque characteristics and promoting aortic wall remodeling in ApoE-/- mice. This study highlights the link between infection-induced inflammation and atherosclerosis progression.
Area of Science:
- Cardiovascular Research
- Infectious Disease Immunology
- Atherosclerosis Pathogenesis
Background:
- Residual inflammation in cardiovascular organs is linked to increased cardiovascular complications post-pneumonia.
- The precise mechanisms by which pneumonia affects cardiovascular health remain incompletely understood.
Purpose of the Study:
- To investigate the impact of Streptococcus pneumoniae infection on plaque characteristics and inflammation in the aorta and heart of ApoE-/- mice.
- To determine if pneumonia contributes to cardiovascular complications through altered plaque stability and aortic remodeling.
Main Methods:
- ApoE-/- mice on a high-fat diet were intranasally inoculated with Streptococcus pneumoniae TIGR4 or PBS.
- Aortic plaque burden and characteristics were assessed using Oil red O and Trichrome staining.
- Inflammatory changes and aortic remodeling were evaluated via FDG-PET imaging and immunofluorescence staining at 2, 7, and 28 days post-infection.
Main Results:
- S. pneumoniae TIGR4 infection led to increased plaque presence in the aortic root and thoracic aorta at specific time points.
- Infected mice exhibited more pronounced aortic wall remodeling at 28 days post-infection.
- Aortic root plaques in infected mice showed reduced collagen and smooth muscle cells, indicating plaque instability.
Conclusions:
- Pneumonia significantly alters plaque burden, plaque characteristics, and aortic wall remodeling in a mouse model of atherosclerosis.
- These Streptococcus pneumoniae-induced cardiovascular changes may explain the heightened risk of cardiovascular complications in pneumonia survivors.
