Gastrin-releasing Peptide Receptor Antagonist RC-3095 Inhibits Porphyromonas Gingivalis Lipopolysaccharide-accelerated Atherosclerosis by Suppressing Inflammatory Responses in Endothelial Cells and Macrophages

Overview

Journal Inflamm Res

Specialties Allergy & Immunology
Pathology

Date 2024 Aug 20

PMID 39164592

Authors

Hyun-Joo Park

Mi-Kyoung Kim

Yeon Kim

Hyung Joon Kim

Hae Ryoun Park

Soo-Kyung Bae

Moon-Kyoung Bae

Affiliations

Soon will be listed here.

Abstract

Objective: Porphyromonas gingivalis (P. gingivalis), one of the major periodontopathogens, is associated with the progression and exacerbation of atherosclerosis. In this study, we aimed to investigate whether the gastrin-releasing peptide receptor antagonist, RC-3095, could attenuate P. gingivalis LPS-induced inflammatory responses in endothelial cells and macrophages, as well as atherosclerosis in an ApoE mouse model treated with P. gingivalis LPS.

Methods: The effect of RC-3095 on P. gingivalis LPS-induced endothelial inflammation was examined using HUVECs and rat aortic endothelium. THP-1 cells were polarized into M1 macrophages by exposure to P. gingivalis LPS, with or without RC-3095. The effect of RC-3095 on atherosclerosis progression was assessed in high-fat-fed male ApoE mice through injections of P. gingivalis LPS, RC-3095, or a combination of both.

Results: RC-3095 significantly reduced P. gingivalis LPS-induced leukocyte adhesion to endothelial cells and aortic endothelium by suppressing NF-κB-dependent expressions of ICAM-1 and VCAM-1. In addition, RC-3095 inhibited the P. gingivalis LPS-induced polarization of M1 macrophages by blocking the MAPK and NF-κB signaling pathways. Moreover, RC-3095 decreased the area of atherosclerotic lesions in ApoE mice, which was accelerated by P. gingivalis LPS injection, and lowered the expressions of ICAM-1 and VCAM-1 in the aortic tissue of mice with atherosclerosis.

Conclusions: RC-3095 can alleviate P. gingivalis LPS-induced endothelial inflammation, macrophage polarization, and atherosclerosis progression, suggesting its potential as a therapeutic approach for periodontal pathogen-associated atherosclerosis.

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