Porphyromonas gingivalis regulates atherosclerosis through an immune pathway

Abstract

Atherosclerosis (AS) is a chronic inflammatory disease, involving a pathological process of endothelial dysfunction, lipid deposition, plaque rupture, and arterial occlusion, and is one of the leading causes of death in the world population. The progression of AS is closely associated with several inflammatory diseases, among which periodontitis has been shown to increase the risk of AS. Porphyromonas gingivalis (P. gingivalis), presenting in large numbers in subgingival plaque biofilms, is the “dominant flora” in periodontitis, and its multiple virulence factors are important in stimulating host immunity. Therefore, it is significant to elucidate the potential mechanism and association between P. gingivalis and AS to prevent and treat AS. By summarizing the existing studies, we found that P. gingivalis promotes the progression of AS through multiple immune pathways. P. gingivalis can escape host immune clearance and, in various forms, circulate with blood and lymph and colonize arterial vessel walls, directly inducing local inflammation in blood vessels. It also induces the production of systemic inflammatory mediators and autoimmune antibodies, disrupts the serum lipid profile, and thus promotes the progression of AS. In this paper, we summarize the recent evidence (including clinical studies and animal studies) on the correlation between P. gingivalis and AS, and describe the specific immune mechanisms by which P. gingivalis promotes AS progression from three aspects (immune escape, blood circulation, and lymphatic circulation), providing new insights into the prevention and treatment of AS by suppressing periodontal pathogenic bacteria.

Periodontitis and hypertension are linked through systemic inflammation: A 5‐year longitudinal study

“…Alternatively, swallowed periodontal bacteria may alter the gut microbiota, enhancing gut epithelial permeability and resulting in endotoxemia, thereby inducing systemic inflammation (Arimatsu et al, 2014). Moreover, periodontal bacteria that enter the bloodstream could invade blood vessel walls and cause endothelial dysfunction by inducing vascular inflammation and oxidative stress (Ruan et al, 2023).…”

The Roles of Periodontal Bacteria in Atherosclerosis

“…However, the application of innovative techniques such as single-cell sequencing and spatial omics in this field remains largely unexplored. The integration of these advanced methodologies is expected to facilitate a more comprehensive understanding of the role of periodontal bacteria in the cellular and intercellular interactions within the AS microenvironment [ 97 ]. Consequently, this will provide crucial theoretical foundations for the prevention and treatment of both periodontal disease and atherosclerosis.…”

“…Pg and its components, including outer membrane vesicles (OMVs), can boost the binding and phagocytosis of macrophages to low-density lipoprotein (LDL), and macrophage-mediated modification of LDL [ 93 ]. Pg can increase the expression of CD36, a scavenger receptor that mediates cholesterol uptake through the c-Jun-AP-1 pathway [ 94 ] or ERK/NF-κB [ 95 ], as well as lysosomal integral membrane protein 2 (LIMP2) involved in cholesterol transport [ 96 , 97 ], so as to intensify the lipid accumulation of macrophages. Pg -infected macrophages up-regulate fatty acid binding protein 4 (FABP4), an intracellular transport protein for fatty acids, presenting more intake of fatty acids [ 98 ].…”

“…Pg also inhibits EC proliferation [ 76 ], promotes EC apoptosis [ 75 , 76 , 77 , 78 ], epithelial–mesenchymal transition [ 65 ], oxidative stress, and inflammatory factor secretion [ 46 , 81 , 82 ], ultimately disrupting the vascular endothelial barrier. Under Pg stimulation, macrophages produce more inflammatory mediators [ 92 ], leading to increased lipid deposition [ 93 , 94 , 95 , 96 , 97 , 98 , 99 ] and exacerbating the inflammatory environment within the plaque. Pg promotes proliferation [ 103 , 107 ], phenotypic transformation [ 100 , 106 , 107 ], and calcification [ 104 ] of VSMCs.…”

Porphyromonas gingivalis Strain W83 Infection Induces Liver Injury in Experimental Alcohol-Associated Liver Disease (ALD) in Mice

“…P. gingivalis has virulence factors, such as gingipains, capsular polysaccharide, fimbriae and out membrane vesicles, which invade host immune responses [7,8]. This bacterium can evade elimination by the complement system [9,10] and can translocate from dental plaque to other organs, either through circulation or oral infection that exacerbates various diseases, such as arthritis, cardiovascular disease, diabetes, and Alzheimer's disease [11][12][13]. P. gingivalis has been considered a confounding risk factor for systemic diseases when not efficiently eliminated by the host.…”