Porphyromonas gingivalis Dihydroceramides Induce Apoptosis in Endothelial Cells

Abstract

Porphyromonas gingivalis dihydroceramides are found in extracts of calculus-contaminated root surfaces, diseased gingival tissue, and atherosclerotic plaques. These ceramides have been shown to promote inflammatory secretory responses in gingival fibroblasts. Little is known about their effects on the vascular system. We tested the hypothesis that P. gingivalis lipids induce apoptosis of human endothelial cells, and investigated the effects of extracted and purified P. gingivalis lipids on human umbilical vein endothelial cells. P. gingivalis phosphoglycerol dihydroceramides induced apoptosis, but not necrosis, in endothelial cells. Early apoptotic cells showed exposure of phosphatidylserine on the cell surface, followed by the cleavage of procaspases 3, 6, and 9. The release of apoptosis-inducing factor was increased, suggesting mitochondrial involvement. Different caspase inhibitors and cAMP elevation blocked DNA fragmentation. Moreover, N-acetylcysteine significantly reduced apoptosis, suggesting a role for reactive oxygen species in this process. Analysis of these data indicates that dihydroceramides may be important virulence factors of P. gingivalis.