Proatherogenic effects of common pathogens on liver, adipose tissue and coronary artery disease
Year: 2013
Type: dissertation
Abstract: Atherosclerotic vascular diseases (ASVDs) affect the heart and circulatory system. One of the most common forms is coronary artery disease (CAD) which may eventually lead to acute coronary syndrome (ACS). ASVDs are currently the leading cause of mortality worldwide, and account for 47% of all deaths in Europe. The underlying mechanism is atherosclerosis, a progressive disease that manifests in several tissues. Common chronic infections, including periodontal disease and Chlamydia pneumoniae, may promote atherosclerosis and are associated with an increased risk of ASVDs. The general aims of this thesis project were to investigate the role of bacteria associated with periodontal disease in CAD, and the mechanisms by which common chronic infections promote proatherogenic alterations. More specifically, we aimed to: I) study the effects of Aggregatibacter actinomycetemcomitans and C. pneumoniae infections on the liver and adipose tissue lipid homeostasis and inflammation status in mice; II) develop and validate a quantitative PCR (QPCR) method to analyze the levels of periodontal disease-associated bacteria in saliva; and III) determine the association between salivary pathogen levels and CAD. The animal studies were conducted in atherosclerosis-susceptible apolipoprotein E-deficient mice. They were infected intravenously with viable A. actinomycetemcomitans and intranasally with viable C. pneumoniae. Consequently, the pathogens were recovered in the liver and C. pneumonia also in the lungs. Both infections induced systemic and hepatic inflammation, which were seen as an elevation of inflammation markers. Chronic C. pneumoniae infection induced hepatic microvesicular formations, which may promote steatosis. The recurrent A. actinomycetemcomitans infection disturbed the lipid homeostasis of adipose tissue: the proportion of saturated fatty acids was increased and that of polyunsaturated fatty acid decreased. The alterations in adipose tissue transcriptomes were depot-specific, and the inguinal adipose tissue was especially prone to inflammation-related responses. Single-copy gene-based QPCR assays were developed for five periodontal disease-associated bacteria: A. actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Treponema denticola, and Tannerella forsythia. The assays were validated in a case-control population including periodontally diseased and healthy subjects, and the diagnostic ability was found to be potent. The association of these pathogens with CAD was determined by analyzing saliva samples from the Parogene cohort (n = 492), consisting of patients with stable CAD, ACS, and no significant CAD as the reference group. All CAD diagnoses were verified by coronary angiography. The increased salivary levels of A. actinomycetemcomitans strongly associated with both stable CAD and ACS. Systemic exposure to the pathogen was seen as elevated serum antibody levels against the pathogen. The findings from the animal study indicate that A. actinomycetemcomitans and C. pneumoniae infections induce inflammation and disturbances in lipid and fatty acid homeostasis in the liver and adipose tissue. The potential tissue dysfunction may further augment the progression of atherosclerosis. The results from the Parogene study demonstrate that high salivary levels and systemic exposure to A. actinomycetemcomitans are associated with the risk of CAD and its acute manifestation. The findings from the thesis study are of common interest, because the studied pathogens are highly prevalent among the general population and their persistence may increase the overall risk of ASVDs.
Source: Työväentutkimus Vuosikirja
Author: Kati Hyvärinen
Language: English
Subfield: Periodontics
Field: Dentistry
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W1495517568