Enhanced expression of endothelin-A receptor in human transplant renal arteriosclerosis

Transplant renal arteriosclerosis (TRA), characterized by concentric neointimal thickening, is one of the major causes of chronic rejection in human kidney transplantation. Endothelin-1 is known to be a powerful vasoconstrictor and a vascular smooth muscle cell mitogen. Previous experimental studies have shown that endothelin-A receptor (ET(A) receptor) is expressed selectively in vascular smooth muscle cells, and is the major mediator of endothelin-1-induced effects. However, ET(A) receptor expression in human renal allografts has not been reported. In this study, we immunohistochemically investigated the expression of ET(A) receptor in relation to the development of TRA, using nine human renal allografts removed due to rejection and ten normal kidneys as controls. In intrarenal arteries of normal kidneys, medial smooth muscle cells showed weak expression of ET(A) receptor. In intrarenal arteries with TRA of human renal allografts, increased expression of ET(A) receptor was found in medial smooth muscle cells, and distinct expression of ET(A) receptor was also detected in smooth muscle cells within the neointima. These results suggest that enhanced expression of ET(A) receptor may induce an increase in the local proliferative and vasoconstrictive effects of endothelin-1 in human renal allografts.