Titanium implants alter endothelial function and vasoconstriction via a protein kinase C-regulated pathway

The application of titanium (Ti) alloy in joint prostheses is a good choice in orthopedic reconstruction. An elevated serum concentration of Ti has been shown in the patients with loosened knee prostheses. The precise actions of elevated Ti on the circulation remain unclear. In this study the maximal contractile responses elicited by phenylephrine in the aortas of rats 4 weeks after Ti alloy implantation and in cultured rat aortas treated with a soluble form of Ti for a period of 18h were significantly decreased as compared with controls. Aortas isolated from rats with Ti alloy implants or aortas treated with a soluble form of Ti had enhanced protein expression of endothelial nitric oxide synthase (eNOS) and protein kinase C (PKC)-alpha and enhanced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Treatment of human umbilical vein endothelial cells (HUVECs) with a soluble form of Ti for 24h dose-dependently increased eNOS protein expression. Short-term treatment of HUVECs with Ti for 1h effectively enhanced the phosphorylation of eNOS, PKC (pan) and ERK1/2. PKC inhibitors RO320432 and chelerythrine effectively inhibited Ti-enhanced phosphorylation of eNOS and PKC (pan). These results indicate that Ti in the circulation may alter endothelial function and reduce vasoconstriction.