12 Jan Genetics and Common Bacteria Affect Atherosclerosis Progression
MedicalResearch.com Interview with:
Caroline Attardo Genco, PhD
Professor Department of Medicine, Section of Infectious Diseases Department of Microbiology
Boston University School of Medicine
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Genco: Atherosclerosis is a common cardiovascular disease associated with heart attack and stroke. Although it has been shown that a diet high in fat as well as exposure to certain bacteria can cause atherosclerosis (the buildup of fats, cholesterol, and other substances on artery walls which can restrict blood flow), we have for the first time identified distinct gene pathways that are altered by these different stimuli. One of these bacteria, Porphyromonas gingivalis, is found in the mouth of humans with periodontal disease. Another is the bacteria Chlamydia pneumoniae, which causes pneumonia. We found that even though these three different stimuli all cause atherosclerosis, the gene pathways are distinct depending upon stimulus. This is the first study that has performed side-by-side comparison of genome-wide gene expression changes to address this issue.
In this study, we used four experimental groups to compare genome-wide expression changes in vascular tissue. The first group was subjected to Porphyromonas gingivalis, while the second group received Chlamydia pneumoniae. The third group was placed on a high-fat Western style diet, while the fourth group was the control group. In collaboration with the Clinical and Translational Science Institute (CTSI) at Boston University, we performed genome-wide microarray profiling and analysis of vascular tissue from all groups to reveal gene pathways altered in vascular tissue by each treatment group.
These findings may explain how specific infections or high-fat diet may cause atherosclerotic plaques to undergo changes that affect their size and stability and may ultimately lead to a heart attack.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Genco: Given the prevalence of diet-induced obesity and infection with Porphyromonas gingivalis and Chlamydia pneumoniae in the general population and the likelihood of co-morbidity of obesity with chronic or recurring infection with these common pathogens, these findings suggest that the development of atherosclerosis in humans is likely more complex and multifactorial than previously appreciated.
Atherosclerotic plaques undergo both progressive and regressive changes, which affect their size and stability. Our gene set expression analysis showed that Chlamydia pneumoniae treatment upregulated the PPAR pathway while Porphyromonas gingivalis treatment downregulated this pathway and thus may indicate a role for Chlamydia pneumoniae in regression and stability of early lesions, while Porphyromonas gingivalis may inhibit plaque regression.
These findings, which currently appear in BMC Genomics, suggest that future therapies for this disease may need to be individualized.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Genco: We are working on developing a model of atherosclerotic plaque regression to test our hypotheses that these two pathogens can have different effects on the regression of vascular plaque. Furthermore, we are interested in testing interventions that alter the PPAR pathway, such as Rosiglitazone, a PPAR agonist that is used clinically to improve insulin sensitivity. Loss of insulin sensitivity is often observed in patients with obesity, which is a contributing factor to the development of atherosclerosis. On a basic science level, we are currently directing our areas of investigation to study the effect of different atherogenic stimuli on systemic innate and adaptive immune responses.