Recombinant human soluble thrombomodulin attenuates FK506-induced endothelial dysfunction through prevention of Akt inactivation.

Abstract

Thrombomodulin (TM), a transmembrane glycoprotein on vascular endothelial cells, is a naturally occurring anticoagulant. Recombinant human soluble TM (rTM), composed of the extracellular domain of TM, also shows anti-coagulant and anti-inflammatory activity, but the effects of rTM on microangiopathy remain unclear. We reported that FK506 induced endothelial dysfunction through inactivation of Akt and extracellular-regulated kinase 1/2 using a three-dimensional culture blood vessel model. In the present study, we examined the effects of rTM on FK506-induced endothelial dysfunction. We found that rTM suppressed FK506-induced endothelial cell death, but not the breakdown of capillary-like tube structures. rTM prevented FK506-induced inactivation of Akt, but not of extracellular-regulated kinase 1/2. Akt inhibition by LY294002 abrogated the preventive effect of rTM on FK506-induced Akt inactivation and the suppressive effect of rTM on FK506-induced cell death. These results suggest that rTM attenuates FK506-induced endothelial dysfunction through prevention of Akt inactivation.

DOI: 10.1016/j.yexcr.2014.02.023

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@article{Eguchi2014RecombinantHS, title={Recombinant human soluble thrombomodulin attenuates FK506-induced endothelial dysfunction through prevention of Akt inactivation.}, author={Ryoji Eguchi and Yoshihiro Fujimori and Masaya Okada and Hiroya Tamaki and Ichiro Wakabayashi and Hiroyasu Ogawa}, journal={Experimental cell research}, year={2014}, volume={323 1}, pages={112-7} }