Gingipains from the periodontal pathogen Porphyromonas gingivalis play a significant role in regulation of Angiopoietin 1 and Angiopoietin 2 in human aortic smooth muscle cells.
Infect Immun. 2015 Aug 17. Epub 2015 Aug 17. PMID: 26283334
Angiopoietin 1 (Angpt1) and angiopoietin 2 (Angpt2) are the ligands of Tyrosine kinase (Tie) receptors, and they play important roles in vessel formation and the development of inflammatory diseases, such as atherosclerosis. Porphyromonas gingivalis is a gram-negative periodontal bacterium that is thought to contribute to the progression of cardiovascular disease. The aim of this study was to investigate the role of P. gingivalis infection in the modulation of Angpt1 and Angpt2 in human aortic smooth muscle cells (AoSMCs). We exposed AoSMCs to wild type (W50 and 381), gingipain mutant (E8 and K1A), and fimbriae mutant (DPG-3 and KRX-178) P. gingivalis and to different concentrations of tumor necrosis factor (TNF). The atherosclerosis risk factor TNF was used as a positive control in this study. We found that P. gingivalis (wild type, K1A, DPG3 and KRX178) and TNF up-regulated the expression of Angpt2 and its transcription factor ETS1, respectively, in AoSMCs. In contrast, Angpt1 was inhibited by P. gingivalis and TNF. However, the RgpA/B mutant E8 had no effect on the expression of Angpt1, Angpt2, or ETS1 in AoSMCs. The results also showed that ETS1 is critical for P. gingivalis induction of Angpt2. Exposure to Angpt2 protein enhanced the migration of AoSMCs but had no effect on proliferation. This study demonstrates that gingipains are crucial to the ability of P. gingivalis to markedly increase the ratio of expressed Angpt2/Angpt1 in AoSMCs, which determines the regulatory role of angiopoietins in angiogenesis and their involvement in the development of atherosclerosis. These findings further support the association between periodontitis and cardiovascular disease.