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

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Molecular Oral Microbiology, 2041-1014, 2020, p. 1–9

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John Wiley & Sons Ltd.

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Abstract

The role of periodontopathogens in inflammatory endothelial dysfunction is not known. This study characterizes a three-dimensional model with human coronary artery endothelial cells on three-dimensional (HCAEC-3D) type I collagen scaffolds to evaluate whether infection with Aggregatibacter actinomycetemcomitans induces a proinflammatory response associated with atherosclerosis. The HCAEC-3D culture was physicochemically characterized with regard to biocompatibility and barrier function. Then, the culture was infected with A. actinomycetemcomitans strain ATCC 29522 at multiplicities of infection (MOIs) of 1:1, 1:10, and 1:100. Cultures without infection and stimulated with A. actinomycetemcomitans lipopolysaccharide were used as controls. The secretion of soluble factors (IL-6, IL-1β, MCP-1, RANTES, MIP-1, IL-8, IL-1α, and TNF-α) was evaluated via flow cytometry; TGF-β1 was evaluated via enzyme-linked immunosorbent assay (ELISA). The adhesion and migration of fluorescent human THP-1 monocytes was evaluated. IL-8, MCP-1, and IL-6 secretion increased in a dose-dependent manner with A. actinomycetemcomitans infection and was significantly greater than that under control treatment. The concentration of TGF-β1 was significantly higher at MOI 1:100 than in controls. Treatment of the 3D cultures with A. actinomycetemcomitans at different MOIs induced significant differences in the adhesion of monocytes to the endothelium compared to the control without infection. Lastly, conditioned media from 3D cultures treated with A. actinomycetemcomitans induced monocyte migration. The effects of IL-8, MCP-1, IL-6, and TGF-β1 on the endothelium indicate the ability of A. actinomycetemcomitans to induce an inflammatory response through a mechanism of monocyte adhesion and migration and endothelial dysfunction.

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Aggregatibacter actinomycetemcomitans, Atherosclerosis, Endothelial cells, Endothelial dysfunction, Endothelial–mesenchymal transition

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