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

Abstract 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 aortasof rats 4 weeks after Ti alloy implantation and in cultured rat aortastreated with a soluble form of Ti for a period of 18 h were significantly decreased as compared with controls. Aortasisolated from rats with Ti alloy implants or aortastreated with a soluble form of Ti had enhanced protein expression of endothelial nitric oxide synthase ( eNOS) and protein kinase C (PKC)-α 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 24 h dose-dependently increased eNOSprotein expression. Short-term treatment of HUVECs with Ti for 1 h effectively enhanced the phosphorylation of eNOS, PKC (pan) and ERK1/2. PKC inhibitors RO320432 and chelerythrineeffectively inhibited Ti-enhanced phosphorylation of eNOSand PKC (pan). These results indicate that Ti in the circulation may alter endothelial function and reduce vasoconstriction.