Page 95 - Read Online

Kozarov et al. Vessel Plus 2020;4:10 I http://dx.doi.org/10.20517/2574-1209.2019.31 Page 9 of 18

The LDL oxidation leads to an increased expression of adhesion molecules such as vascular cell adhesion
molecule-1, intercellular adhesion molecule-1 and E-selectin on the activated endothelia. This results in
the tethering of the leukocytes to the endothelia, adhesion and diapedesis (extravasation) into the vascular
wall [Figure 1] [114-116] . Thus, in a vicious circle, oxidative stress multiplies the effects of inflammation and
[117]
accelerates the atherogenesis .

In another deleterious activity, the periodontal infection itself accelerates lipid deposition and
atherosclerosis in animal models [118,119] , and therefore addressing the infection would - as an important
added benefit - suppress the atherogenic effects of dyslipidemia.

Atherogenic dyslipidemia (hypercholesterolaemia and hyperlipidaemia) is defined as high plasma LDL and
low plasma HDL cholesterol with elevated triglycerides. The increase of triglyceride and LDL cholesterol
levels include alterations observed in lipid metabolism and lipoprotein composition. Infection and the
concomitant inflammation induce acute-phase response contributing to atherogenic changes in lipid and
[120]
lipoprotein metabolism .

An early and consistent effect of infection/inflammation is increased serum triglyceride level, characterized
by an increase in very low-density lipoprotein (VLDL) levels [121,122] . High bacterial lipopolysaccharide serum
[123]
activity (endotoxemia) has shown a strong correlation with serum triglyceride concentrations (P < 0.001) .
The increase in serum triglycerides may be due to both an increase in hepatic VLDL production and a
[124]
decrease in the clearance of triglyceride rich lipoproteins in chronic inflammation .

[122]
Endotoxemia also modulates HDL composition and size . HDL is one of the plasma lipoproteins that
neutralize Gram-negative bacterial LPS and Gram-positive bacterial lipoteichoic acid, thus favoring the
clearance of these products [125] . For example, the mean percentage of HDL cholesterol in Helicobacter
pylori-seropositive patients was significantly lower than the one measured in seronegative ones (P = 0.008
[126]
and P < 0.001, respectively) . In another study, the Health 2000 Health Examination Survey, which
included 8028 Finnish subjects aged 30 or older, no consistent association between serum lipid levels
and periodontal infection among normoweight subjects was found. However, an association was found
[127]
of high serum triglycerides and low HDL with periodontal infection among obese subjects . Overall,
these authors were not able to present evidence that unfavorable lipid composition can be considered as an
[128]
important risk for periodontal infection in a general adult population .
Specifically, for periodontal infections, both total and LDL-cholesterol were significantly associated with
[129]
antibody titer to P. gingivalis in non-obese patients . The latest meta-analysis suggested that periodontitis
is significantly associated with reduced HDL (P = 0.0005), elevated LDL (P = 0.003) and triglycerides (P <
0.0001) compared to healthy controls, supporting the rationale that periodontal disease is associated with
[130]
lipid metabolic control .
Effect of periodontal treatment on atherosclerotic inflammation
Due to the extended amount of time during which the atherogenesis takes place and even more to obvious
ethical reasons, it is virtually impossible to obtain an unambiguous demonstration of the effectivity of
antibacterial treatment on atherosclerotic inflammation. This however should not prevent from exploring
the alternative approaches to examine attenuation and moreover, reversal of atherogenesis via resolution of
the vascular inflammation.

Current therapeutic strategies focus on anti-inflammation, i.e., on pharmacologic intervention in
the inflammatory pathways. However, only resolution of inflammation will restore the homeostasis.
The isolation and characterization of resolving agonist molecules using endogenous lipid mediators