Direct or indirect endothelial cell transforming growth factor-β receptor activation initiates arteriolar hyalinosis.

Abstract

Tacrolimus (FK-506) controls organ rejection; however, arteriolar hyalinosis is a frequent complication. By use of mice lacking FK-506-binding protein-12 in endothelial cells, Chiasson and co-workers explored the contribution of endothelial cells and the transforming growth factor-β pathway to define mechanisms of hyalinosis. Absence of this binding protein removed a tonic inhibition to activate the transforming growth factor-β system, causing arteriolar hyalinosis. However, tacrolimus can have effects on any biologic process involving receptors with a GS domain.