Impact of a CD36 inhibitor on Porphyromonas gingivalis mediated atherosclerosis.

Abstract

OBJECTIVE:

To determine if AP5055 drug, an inhibitor of CD36, prevents the increase in Porphyromonas gingivalis (P. gingivalis) mediated atherosclerosis in low-density lipoprotein receptor knockout (LDLR KO) mice by targeting CD36.

METHODS:

Male LDLR KO mice were infected with P. gingivalis by oral lavage to induce periodontal disease and fed a western diet to induce atherosclerosis. Mice were treated with the CD36 inhibitor, AP5055 (1 mg/kg), or vehicle (1% DMSO). Aortae were dissected and stained with oil red-O for morphometric analysis; blood/plasma was collected to determine markers of inflammation by cytokine array and cholesterol levels. P. gingivalis-induced bone loss in mandibles was assessed using micro-CT. P. gingivalis lipopolysaccharide stimulated nuclear factor-kappa B (NF-κB) activity was measured using a reporter gene (secreted alkaline phosphatase) assay in AP5055 treated or untreated RAW-Blue macrophages.

RESULTS:

Isolated aortae showed a significant decrease in lesion area in the AP5055 treated group as compared to the control group. Mechanistically, in vitro analysis demonstrated that AP5055 inhibited NF-κB activity. Cytokine array showed a decrease in the expression of pro-inflammatory cytokines and decreased levels of plasma cholesterol in AP5055 treated mice. Micro-CT measurements of bone loss were not significant between the two groups.

CONCLUSION:

CD36 inhibitor AP5055 abrogates atherosclerotic lesion burden associated with periodontal disease, accompanied by a reduction in markers of inflammation. These experiments may support the development of drugs targeting CD36 for human disease.

• Authors: Umar Rauf Rekhi, Raisa Queiroz Catunda, Maria Alexiou, Monika Sharma, Aaron Fong, Maria Febbraio
• Journal: Archives of oral biology (Arch Oral Biol) Vol. 126 Pg. 105129 (Jun 2021) ISSN: 1879-1506 [Electronic] England
• PMID: 33934042 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• CD36 Antigens
• Lipopolysaccharides
• NF-kappa B

Topics

• Animals
• Atherosclerosis
• CD36 Antigens
• Lipopolysaccharides
• Male
• Mice
• NF-kappa B (metabolism)
• Porphyromonas gingivalis (metabolism)