LAUSR

Porphyromonas (P.) gingivalis infection leading to the periodontitis has been associated with the development of systemic diseases, including cardiovascular diseases and diabetes. However, the effect of a high concentration of glucose (HG) on the invasion efficiency of P. gingivalis and the consequent modulation of pathogenesis in vascular cells, especially in the vascular smooth muscle cells (VSMCs), remains unclear. Hence, the aim of this study was to investigate whether treating P. gingivalis with HG could change its invasion capability and result in VSMC calcification and the underlying mechanism. Human aortic SMCs (HASMCs) and P. gingivalis strain CCUG25226 were used in this study. We found that HGPg infection of HASMCs could initiate the HASMC calcification by stimulating the autocrine regulation of bone morphogenetic protein (BMP) 4 in HASMCs. The upregulation of BMP4 expression in HASMCs was mediated by toll‐like receptor 4 and ERK1/2‐p38 signaling after P. gingivalis infection. Moreover, the autocrine action of BMP4 in HGPg infection‐initiated HASMC calcification upregulated BMP4‐specific downstream smad1/5/8‐runx2 signaling to increase the expressions of bone‐related matrix proteins, that is, osteopontin, osteocalcin, and alkaline phosphatase. This study elucidates the detailed mechanism of HGPg infection‐initiated calcification of HASMCs and indicates a possible therapeutic role of BMP4 in P. gingivalis infection‐associated vascular calcification.