Two‐dimensional and three‐dimensional models for studying atherosclerosis pathogenesis induced by periodontopathogenic microorganisms

Abstract

Epidemiological studies have established a clinical association between periodontal disease and atherosclerosis. Bacteremia and endotoxemia episodes in patients with periodontitis appear to link these two diseases by inducing a body-wide production of cardiovascular markers. The presence of oral bacteria in atherosclerotic lesions in patients with periodontitis suggests that bacteria, or their antigenic components, induce alterations in the endothelium associated with atherosclerosis. Therefore, a causal mechanism explaining the association between both diseases can be constructed using in vitro models. This review presents current experimental approaches based on in vitro cell models used to shed light on the mechanism by which periodontal pathogenic microorganisms, and their antigenic components, induce proatherosclerotic endothelial activity. Monolayer cultures of endothelial vascular or arterial cells have been used to assess periodontal pathogenic bacteria and their antigenic compounds and endothelial activation. However, these models are not capable of reflecting the physiological characteristics of the endothelium inside vascularized tissue. Therefore, the shift from two-dimensional (2D) cellular models toward three-dimensional (3D) models of endothelial cells resembling an environment close to the physiological environment of the endothelial cell within the endothelium is useful for evaluating the physiological relevance of results regarding the endothelial dysfunction induced by periodontopathogens that are currently obtained from 2D models. The use of in vitro 3D cellular models can also be relevant to the search for therapeutic agents for chronic inflammatory diseases such as atherosclerosis. Here, we present some strategies for the assembly of 3D cultures with endothelial cells, which is useful for the study of periodontopathogen-mediated disease.

Differential responses of endothelial cells on three‐dimensional scaffolds to lipopolysaccharides from periodontopathogens

“…The culture of ECs on the surface of type I collagen scaffolds exposes them to a component of the subendothelium of blood vessels. However, ECs seeded on 3D scaffolds made with proteins found in the subendothelial ECM have not been used to assess the effect of periodontopathogens on cultured ECs (Gualtero, Lafaurie, & Fontanilla, ). For that reason, in the present work, a model was developed by seeding human coronary artery endothelial cells (HCAECs) onto 3D scaffolds of type I collagen adhered to the apical surface of the apical chamber of cell culture inserts.…”

Periodontal pathogens and their role in cardiovascular outcome

“…An association between cardiovascular (CV) and periodontal diseases has been highlighted in several epidemiological studies (Beukers, Heijden, Wijk, & Loos, ; Gualtero, Lafaurie, & Fontanilla, ; Humphrey, Fu, Buckley, Freeman, & Helfand, ; Kholy, Genco, & Dyke, ; Nazir, ; Reichert et al, ; Tonetti, Van Dyke, & working group 1 of the joint EFP/AAP workshop, ). The relationship between both diseases is based on biological plausibility (Gualtero et al, ; Kholy et al, ; Wallet, Puri, & Gibson, ).…”

Aggregatibacter actinomycetemcomitans induces a proatherosclerotic response in human endothelial cells in a three‐dimensional collagen scaffold model

“…HCAECs cultured on three-dimensional (3D) type I collagen scaffolds show different inflammatory responses to periodontopathogenic LPS compared to conventional cultures on polystyrene plates (Gualtero et al, 2018). These studies suggest that the substrate on which cells grow modifies the endothelial response observed in vitro against pathogens.…”