Cardiovascular changes after pneumonia in a dual disease mouse model

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.

Pneumonia-Induced Inflammation, Resolution and Cardiovascular Disease: Causes, Consequences and Clinical Opportunities

“…[36][37][38][39][40] ApoE (apolipoprotein E)-deficient mice (a well-established animal model of atherosclerosis) that survived experimental Nonstandard Abbreviations and Acronyms bacterial sepsis showed accelerated progression of their aortic atheromas, increased inflammatory activity within their atheromatous plaques, and increased systemic inflammatory activity up to 5 months after their infectious challenge compared with uninfected animals. 41 Similar acceleration of atherosclerosis and increased intraplaque inflammation post-infection has been described in ApoE-deficient mice with experimental S pneumoniae pneumonia that were rescued with antibiotics 42 or that recovered spontaneously from this 43 and other infectious challenges such as infection with Chlamydophila pneumoniae (another common bacterial cause of pneumonia in humans) [44][45][46] or influenza virus. 47 Possible explanations for the heightened inflammation observed in animal models of infection and atherosclerosis include the direct infiltration of the atheromatous tissue by the infection-causing microbe or the indirect proatherogenic effect of species-specific microbial toxins.…”

“…58 Atherosclerosis-prone mouse models of S pneumoniae pneumonia (ranging from severe infection requiring antibiotic rescue to mild infection) demonstrated increased atherosclerotic plaque progression and accumulation of macrophages compared with noninfected mice. 42,43 Other mediators of inflammation also persist following lung infection, which could contribute to inflammation in the atherosclerotic plaque. Bacterial pneumonia in humans and mice results in elevated levels of cardiolipin-a mitochondrial damage-associated molecular protein that promotes posttranscriptional modifications of PPARγ (peroxisome proliferator-activated receptor gamma), which blocks IL-10 synthesis.…”

A multiple comorbidities mouse lung infection model in ApoE‑deficient mice

“…After 8 weeks of a HFD, atherosclerotic plaques were evident in the aortic arch of ApoE -/mice (Fig. S1), as previously described (12). All animal experiments and procedures were approved by the local Ethics Committees of Harry Perkins Institute of Medical Research, Perth, Australia (approval no.…”

“…The model is relevant to the study of pneumonia infections and characterisation of lung and systemic changes that occur following an episode of pneumonia in the context pre-existing atherosclerosis. This multiple comorbidity murine model will be useful in assessing cardiovascular risk following exposure to S. pneumoniae -caused pneumonia ( 12 ).…”

Rational Design of a Double-Locked Photoacoustic Probe for Precise In Vivo Imaging of Cathepsin B in Atherosclerotic Plaques

“…It triggers inflammation, leading to cytokine release, oxidative stress, and increased risk of plaque rupture, heart attack, and stroke. Thus, close monitoring and management of cardiovascular risk factors during acute pneumonia is crucial. ,, Specifically, ApoE –/– mice were fed on a high-fat diet for 14 weeks to obtain AS mice. To obtain the AS mice complicated with the pneumonia model, AS mice received 50 μg of LPS intranasally twice a week ( n = 3) (Figure g).…”