Page 92 - Read Online

Page 6 of 18 Kozarov et al. Vessel Plus 2020;4:10 I http://dx.doi.org/10.20517/2574-1209.2019.31

hemagglutinin domain of P. gingivalis), and Aa-HSP60 (heat shock protein 60 of A. actinomycetemcomitans)
were discovered to be elevated in stable-CAD and acute coronary syndrome patients when compared to
[60]
CAD-healthy subjects . Periodontal patients were characterized by higher levels of subgingival bacteria.
The serum IgA/IgG burden indicated higher risk for acute coronary syndrome (OR = 1.84, 95%CI: 1.01
to 3.35 for IgA; OR = 1.87, 95%CI: 1.01 to 3.46 for IgG). This risk was independent of other cardiovascular
[61]
risk factors (body mass index, number of teeth, subgingival bacterial levels and periodontal diagnosis) .
The serological differences in periodontitis patients may present risk factors for atherosclerosis. These
seroepidemiological findings are consistent with an association between periodontitis and cardiovascular
disease.

Association of bacteria with atheromatous tissue
Identification of periodontal pathogens in vascular tissue. While oral tissues are the primary sites
for P. gingivalis infection, it has been long shown it can also enter the circulation daily through the
microvasculature following tooth brushing and other dental procedures . Routine procedures such
[62]
as tooth extraction may also lead to transient bacteremia [63-65] . Periodontal biofilm bacteria are thus
disseminated to large vessels. Consequently, bacterial DNA was detected in atheromas by PCR where
[66]
[67]
P. gingivalis was the most abundant pathogen compared to all others tested species . Similarly, a high
content of periodontal pathogens were detected in atheromatous arterial specimens from atherosclerosis
patients. The pathogens were specifically detected within primary atheromatous lesions. Critically, most
patients had severe periodontitis .
[68]
Using reverse transcription polymerase chain reaction, DNA from endodontic bacteria was identified in
20/36 (56%) of aortic aneurism tissue specimens and DNA from periodontal bacteria in 17/36 (47%) of
[69]
these specimens . Compared to cardiac bypass control samples, both ruptured and unruptured aneurysm
[70]
specimens presented significantly more bacterial DNA (P = 0.003 and 0.001, respectively) . Further,
quantitation of DNA from periodontopathic bacteria using universal and species-specific TaqMan probe/
primer sets demonstrated total bacterial DNA in 94.9%, and periodontopathic bacterial DNA in 92.3 %
[71]
of the atherosclerotic plaques from periodontal disease patients . Using sequence analysis of bacterial
16S rRNA libraries from atherosclerotic plaques, 23 bacterial species/phylotypes were identified, where 15
(60.9%) of the phylotypes were reported as yet uncultivable or as yet uncharacterized species . P. gingivalis
[72]
[73]
DNA was found in 21 of 91 (23%) samples taken from carotid endarterectomies .
More importantly, live invasive periodontal pathogens, P. gingivalis and A. actinomycetemcomitans were
[74]
identified in a patient plaque . In the same line of investigation, a large number of strains were cultivated
from patient plaques, belonging to different species, mostly associated with periodontal biofilm, including
P. gingivalis [75,76] . It will also be interesting to adapt to atheromas the recently communicated reverse-
[77]
genomics-enabled cultivation and characterization of as-yet-uncultured species .

It has also been shown that more than 90% of all infections in the head and neck region can have an
odontogenic origin . Most recently, P. gingivalis proteinase gingipain was detected in 96% of the 53
[78]
[79]
brain tissue sections from Alzheimer’s patients , indicating overall systemic hematogenous spread of
periodontal bacteria.

Effects of bacterial infection of vasculature
A variety of communications on animal experiments have suggested that bacterial infection may
predispose to early atherosclerosis and plaque instability . In addition to passive dissemination by
[80]
[81]
way of the bloodstream, bacteria may disseminate and cause low-grade focal infections due to their
ability to invade and persist intracellularly. Low-grade infection presents mixed positive/negative results
for infection, inflammation or pathogen identification since it requires prolonged culturing. Thus, using