J Periodontal Implant Sci.  2018 Feb;48(1):60-68. 10.5051/jpis.2018.48.1.60.

Porphyromonas gingivalis accelerates atherosclerosis through oxidation of high-density lipoprotein

• Kim HJ
• Cha GS
• Kim HJ
• Kwon EY
• Lee JY
• Choi J
• Joo JY

• KMID: 2405410
• DOI: http://doi.org/10.5051/jpis.2018.48.1.60

Abstract

PURPOSE
The aim of this study was to evaluate the ability of Porphyromonas gingivalis (P. gingivalis) to induce oxidation of high-density lipoprotein (HDL) and to determine whether the oxidized HDL induced by P. gingivalis exhibited altered antiatherogenic function or became proatherogenic.
METHODS
P. gingivalis and THP-1 monocytes were cultured, and the extent of HDL oxidation induced by P. gingivalis was evaluated by a thiobarbituric acid-reactive substances (TBARS) assay. To evaluate the altered antiatherogenic and proatherogenic properties of P. gingivalis-treated HDL, lipid oxidation was quantified by the TBARS assay, and tumor necrosis factor alpha (TNF-α) levels and the gelatinolytic activity of matrix metalloproteinase (MMP)-9 were also measured. After incubating macrophages with HDL and P. gingivalis, Oil Red O staining was performed to examine foam cells.
RESULTS
P. gingivalis induced HDL oxidation. The HDL treated by P. gingivalis did not reduce lipid oxidation and may have enhanced the formation of MMP-9 and TNF-α. P. gingivalis-treated macrophages exhibited more lipid aggregates than untreated macrophages.
CONCLUSIONS
P. gingivalis induced HDL oxidation, impairing the atheroprotective function of HDL and making it proatherogenic by eliciting a proinflammatory response through its interaction with monocytes/macrophages.

Keyword

Atherosclerosis; Cardiovascular diseases; Cholesterol; Periodontitis; Porphyromonas gingivalis

MeSH Terms

Atherosclerosis*
Cardiovascular Diseases
Cholesterol
Foam Cells
Lipoproteins*
Macrophages
Monocytes
Periodontitis
Porphyromonas gingivalis*
Porphyromonas*
Thiobarbituric Acid Reactive Substances
Tumor Necrosis Factor-alpha
Cholesterol
Lipoproteins
Thiobarbituric Acid Reactive Substances
Tumor Necrosis Factor-alpha

Figure

• 

  Figure 1 Quantification of Porphyromonas gingivalis-induced HDL oxidation using a TBARS assay.HDL: high-density lipoprotein, TBARS: thiobarbituric acid-reactive substances, Control: sample without HDL and Porphyromonas gingivalis, P.g.: Porphyromonas gingivalis.a)Statistically significant (P<0.01).

• 

  Figure 2 TBARS analysis of LDL incubated with CuSO4 and HDL in the presence and absence of Porphyromonas gingivalis.LDL: low-density lipoprotein, HDL: high-density lipoprotein, Control: sample without LDL, HDL, and Porphyromonas gingivalis, P.g.: Porphyromonas gingivalis, TBARS: thiobarbituric acid-reactive substances.a)Statistically significant (P<0.05); b)Statistically significant (P<0.01); c)Statistically significant (P<0.001).

• 

  Figure 3 Proinflammatory activity by Porphyromonas gingivalis-induced oxidized HDL. (A) Monocytes incubated with Porphyromonas gingivalis in the presence of HDL produced significantly higher levels of TNF-α than monocytes treated with CuSO4 or with HDL alone. (B) Monocytes incubated with Porphyromonas gingivalis and HDL showed higher MMP-9 activity than cells incubated with HDL alone.HDL: high-density lipoprotein, TNF-α: tumor necrosis factor alpha, MMP: matrix metalloproteinase, P.g.: Porphyromonas gingivalis, Control: sample without Porphyromonas gingivalis.a) Statistically significant (P<0.05); b)Statistically significant (P<0.001).

• 

  Figure 4 Macrophage foam cell formation assessed by Oil Red O staining. The uptake of oxidized HDL by macrophages treated with (A) HDL only, (B) HDL oxidized with Porphyromonas gingivalis, and (C) HDL oxidized with CuSO4 was determined by light microscopy (scale bar=200 μm).HDL: high-density lipoprotein.

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