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Discovery of Atherosclerosis Microbiome: Systems Biology of Cardiovascular Pathogenesis

Final Report Summary - CARDIOMICROBIOME (Discovery of Atherosclerosis Microbiome: Systems Biology of Cardiovascular Pathogenesis)

We may now have a long-awaited approach to heart attack and stroke

Investigators Find Promising Drug Targets in Atherosclerotic Plaque Tissues

– The same plaque that is clogging the arteries of people with atherosclerosis and other forms of cardiovascular disease, causing heart attack and stroke may have a direct link to pathogenic bacteria, many of which dwell in the mouth, Dr. Emil Kozarov’s team has found.

Furthering his pioneering research into whether bacteria play a direct role in atherosclerosis, Dr. Emil Kozarov and an interdisciplinary team of scientists set out to culture and identify several bacterial species from the atherosclerotic tissue of aseptic patients undergoing surgery for arterial obstruction.

Some of the bacteria, the researchers found, could be traced back to species that typically originate in the mouth – such as the bacterium Porphyromonas gingivalis, the precursor and a major culprit in periodontitis. Unlike in the mouth, however, these bacteria in the arteries keep low profile, causing low grade inflammation until a heart attack or stroke occurs via triggering mechanism that is not completely understood yet. Gut flora bacteria have also been identified and cultured.

According to his findings, published or submitted for publication in medical research journals, atherosclerotic tissue samples reveal a flora of bacteria heretofore unassociated with atherosclerotic lesions. Some of these bacteria are highly responsive to antibiotics and so the thinking is that relatively common anti-microbials (such as doxycycline, or vancomycin) can be enlisted to fight the development of plaque in arterial tissue, Dr. Kozarov said.

Dr. Kozarov and his team recovered a limited number of bacterial species from tissues from the studied patients. Using biochemical analyses, DNA sequencing and databases, so far they identified such species as Propionibacterium acnes, Staphylococcus epidermidis, Streptococcus infantis and Porphyromonas gingivalis. The recovered bacteria are known to induce blood clotting. The presence of these bacteria suggests they may play a key role in vascular pathogenesis, specifically atherosclerosis, or what is commonly referred to as “clogging of the arteries.”

Atherosclerosis is a chronic inflammatory condition associated with hypertension, hyperlipidemia, diabetes and smoking. “Although it has been shown that these conventional risk factors are prevalent among individuals with cardiovascular disease, the incidence of atherosclerosis is not fully explained by them,” Dr. Kozarov said. “The mechanisms involved in atherogenesis resemble protection from microbial assault. A mountain of epidemiological data suggests that chronic infectious diseases, often periodontitis or intestinal inflammations, may be a strong contributing factor in the development of atherosclerotic plaques.”

In the latest study, genomic analysis of diseased tissue and matching healthy tissue from the same individual identified a higher presence of bacteria in the diseased tissue. The data suggest that chronic infection underlie the process of atherogenesis and that it can be initiated by the systemic dissemination of bacteria though different “gates” such as inflamed gums or gut. The data also support Dr. Kozarov’s previous studies, in which his team identified periodontal bacteria in carotid arteries, thus pointing to tissue-destroying periodontal infections as one possible entry to the body’s cerebrovascular system.

“So far the medical science had mostly bacterial ‘fingerprints’ at the crime scene. Now we have the ‘smoking gun,’” Dr. Kozarov said. “This advancement allows us to design entirely novel companion diagnostics assays for primary and secondary prevention of heart attack and stroke, and we will next consider novel therapeutics and treatment regimens.” Investigating the impact of the bacteria play, and which are the prevalent species at the diseased vascular sites “will open the possibility to address atherosclerosis in an expedited manner, using personalized medicine approach to respond to the dire need of reducing governments’ healthcare budgets without compromising the health of the population”, continued Dr. Kozarov.

Dr. Kozarov’s team is now applying for government and pharma grants to develop prototypes for particularly promising applications, and is open to collaborations with companies involved in diagnostics of chronic diseases. Recent grantee of the Marie Curie Programme at the Institute for Cardiovascular Sciences in Barcelona, Dr. Kozarov can be reached at EKozarov@gmail.com.