Exosomes of Porphyromonas gingivalis-Infected Macrophages Impair the Endothelial Barrier and Angiogenesis In Vitro.

OBJECTIVES

Endothelial dysfunction is a key contributor to periodontal disease and apical periodontitis. However, the role of macrophages in mediating endothelial function via exosomes in these inflammatory diseases remains elusive.

MATERIALS AND

METHODS

Exosomes isolated from Porphyromonas gingivalis (P.g)-infected THP-1-derived macrophages (P.g-Exos) and uninfected macrophages (Con-Exos) were verified and their effects on human umbilical vein endothelial cells (HUVECs) were investigated. The expression of TNF-α and IL-6 in HUVECs was tested by quantitative real time PCR (qRT-PCR) and ELISA. A fluorescein isothiocyanate (FITC)-dextran leakage assay and a THP-1 monocyte adhesion assay were used to explore vascular permeability and cellular adhesion. The migration and angiogenic capacity were evaluated using transwell, cell scratch, and tube-forming assays. HUVECs were pretreated with SC79 (Akt activator) to explore the mechanism.

RESULTS

P.g stimulation increased the release of exosomes from macrophages. P.g-Exos inhibited HUVECs' migration and tube formation capabilities while increasing vascular permeability, promoting leukocyte adhesion and releasing proinflammatory factors. Importantly, P.g-Exos induced endothelial dysfunction partially via the Akt/mTOR pathway suppression.

CONCLUSIONS

Summarily, this study reveals that the exosomes derived from inflammatory macrophages mediate HUVECs dysfunction partially via the Akt/mTOR pathway, providing novel insights into potential treatments for oral inflammatory diseases.