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Page 12 of 18 Kozarov et al. Vessel Plus 2020;4:10 I http://dx.doi.org/10.20517/2574-1209.2019.31

Evidence supporting this view is several-fold: (1) epidemiological data support an infectious component in
atherosclerosis; (2) atherosclerosis has many of the characteristics of a chronic infectious disease; and (3)
[165]
internalization of bacteria can produce a “privileged niche” (i.e., shelter from immune response and drugs) .
Of note, a variety of species, mostly with periodontal origin were cultivated from atheromatous tissue
of endarterectomy patients [74-76] . These are promising targets for intervention, specifically P. gingivalis,
a gram-negative anaerobe capable of invading a variety of non-phagocytic eukaryotic cells [166-170] . P.
[171]
gingivalis is a key periodontal pathogen causing inflammation and host tissue destruction. It becomes
[105]
internalized and also persists in vascular cells . While oral tissues are the primary sites for P. gingivalis
infection, it can also enter the circulation daily through the microvasculature and its role in periodontitis
[30]
is established . Most importantly, an invasive P. gingivalis strain accelerated atherosclerosis in a murine
[84]
[45]
model and as mentioned before its tissue invasion ability was critical for atherosclerosis progression .
These advancements pave the way for further promising developments along the Alzheimer’s treatment
[79]
technology where P. gingivalis is identified as a key target .
Addressing the atherosclerosis microbiome: a new approach to CVD risk modification
The cultivation and identification in atheromatous plaques of a variety of viable bacteria suggests that
atherosclerotic lesions can be induced or exacerbated by these inflammatory pathogens. Importantly, it was
shown that bacteria not only invaded both vascular cell types but also persisted intracellularly. Moreover,
the bacteria were transmitted between both cell types and to healthy cells, explaining the chronicity of
[172]
[105]
infection . Such intracellular polymicrobial flora has been well demonstrated , pointing to a plausible
[173]
contributor to premature atherosclerosis .
A natural approach to restore the homeostasis is reversing the atherogenic process, via control of the
inflammatory component, often originating from periodontal lesions. An important advantage of such
approach is that the main problem in medical care can be addressed as initiated or exacerbated by
prokaryotes. Targeting bacteria, thus minimizing the side effects of treatment, is inherently more attractive
than the current complicated designs addressing metabolic pathways.

Moreover, the infection itself accelerates lipid deposition and atherosclerosis in animal models [118,119] , and
therefore addressing the infection would also suppress the effects of hyperlipidemia.

A variety of available methodologies can be adapted to bring about development of vaccines and small
molecule inhibitors of the identified pathogens. The emergence of infections, specifically from periodontal
origin as a potential risk factor for CVD, is leading to a convergence in oral and medical care that will
hopefully benefit the patients and public health .
[174]

DECLARATIONS
Authors’ contributions
Wrote and reviewed the manuscript: Kozarov E, Progulske-Fox A

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.