Emil Kozarov and a team of researchers at the Columbia University College of Dental Medicine have identified specific bacteria that may have a key role in atherosclerosis, or what is commonly referred to as “hardening of the arteries,” caused by plaque build-up, which can lead to heart attack and stroke.
Fully understanding the role of bacterial infections in cardiovascular diseases has been challenging because researchers have previously been unable to isolate live bacteria from plaque tissue removed from the arteries. Using specimens from the Department of Surgery and the Herbert Irving Comprehensive Cancer Center at Columbia University, Kozarov and his team, however, were able to isolate bacteria from a 78-year-old male who had previously suffered a heart attack. Their findings are explained in the latest Journal of Atherosclerosis and Thrombosis.
In the paper, researchers describe using cell cultures to study the genetic make-up of the tissue and to look for the presence of bacteria that could be cultured and grown for analysis. In addition, they looked at five pairs of both diseased and healthy arteries. Culturing the cells aided in the isolation of the bacillus Enterobacter hormaechei from the patient’s tissue. Implicated in bloodstream infections such as sepsis and other life-threatening conditions, the isolated bacteria were resistant to multiple antibiotics. Surprisingly, this microbe was further identified in very high numbers in diseased but not in healthy arterial tissues.
The data suggest that a chronic infection may underlie the process of atherosclerosis, an infection that can be initiated by the spread of bacteria though different “gates” in the vascular wall—as in the case of someone with an intestinal infection. The data support Kozarov’s previous studies, where his team identified bacteria normally found in a person’s mouth and in the carotid artery, thus pointing to tissue-destructing periodontal, or tooth and gum, infections as one possible gate to the circulation.
Bacteria can gain access to blood vessels through different avenues, and then penetrate their vascular walls where they can create secondary infections that have been shown to lead to plaque formation, the researchers continued. “In order to test the idea that bacteria are involved, we must be able not only to detect bacterial DNA, but first of all to isolate the bacterial strains from the vascular wall from the patient,” Kozarov said.
One specific avenue of infection the researchers studied involved bacteria getting access to the circulatory system via white blood cells (phagocytes) designed to ingest harmful foreign particles. The model that Kozarov’s team was able to demonstrate showed an intermediate step where Enterobacter hormaechei is internalized by the phagocytic cells, but a step wherein bacteria are able to avoid immediate death in phagocytes. Once in circulation, Kozarov said, bacteria using this “Trojan horse” approach can persist in the organism for extended periods of time while traveling to and colonizing distant sites such as the carotid, femoral artery or the aorta. This can lead to failure of antibiotic treatment and initiation of an inflammatory process, or atherosclerosis.
“Our findings warrant further studies of bacterial infections as a contributing factor to cardiovascular disease,” said Kozarov, an associate professor of oral biology at the College of Dental Medicine. Jingyue Ju
, co-author and director of the Columbia Center for Genome Technology & Biomolecular Engineering, also contributed to this research, which was supported in part by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by the Columbia University Section of Oral and Diagnostic Sciences. “The concept that bacteria might not face an immediate death after being ingested by white blood cells likely contributes to the spread of potentially plaque-forming bacteria to sites where they might not normally be present.”