ADAMTS13-marker of contractile phenotype of arterial smooth muscle cells lost in benign nephrosclerosis

作者：Bockmeyer Clemens L; Forstmeier Vinzent; Modde Friedrich; Lovric Svjetlana; Claus Ralf A; Schiffer Mario; Agustian Putri A; Grothusen Christina; Grote Karsten; Birschmann Ingvild; Theophile Katharina; Kreipe Hans H; Broecker Verena; Becker Jan U^*

来源：Nephrology Dialysis Transplantation, 2011, 26(6): 1871-1881.

DOI：10.1093/ndt/gfq604

• arterial hypertension
• arterioles
• hypertensive nephrosclerosis
• kidney
• sm-MHC

Background. Hypertensive nephrosclerosis alone and in combination with other renal diseases is a leading cause of terminal renal insufficiency. Histologic lesions manifest as benign nephrosclerosis (bN) with arteriolar hyalinosis and later fibrosis. Procoagulant micromilieus have been implicated in fibrosis. Hyalinosis is considered to consist of plasma insudation possibly containing procoagulant factors like von Willebrand factor (VWF). Therefore, it is hypothesized that VWF cleaving protease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type-1 motif, 13) is normally expressed by arteriolar vascular smooth muscle cells (VSMCs) and diminished in bN and that this reduction contributes to fibrosis in bN.
Methods. ADAMTS13 expression was examined by immunohistochemistry and quantitative real-time polymerase chain reaction in VSMCs of various human organs. Fifty-four specimens with and seven without bN were immunostained for ADAMTS13, VWF, CD61 and VSMC differentiation markers in arteriolar walls.
Results. Expression of ADAMTS13 is confirmed in VSMCs. In bN, ADAMTS13 immunostaining of arterial VSMCs correlated inversely with fibrotic but not hyalinotic lesions. Smooth muscle myosin heavy chain showed an inverse correlation with hyalinotic, as opposed to fibrotic lesions of bN. Smoothelin showed an inverse correlation with both hyalinotic and fibrotic lesions of bN. VWF was absent in normal controls and hyalinotic lesions, but present exclusively in fibrotic lesions in 7/54 (13%) bN cases. CD61 was absent in all arteriolar walls.
Conclusions. The present results establish ADAMTS13 as a novel marker of contractile VSMCs that is retained in early hyalinotic bN but partially lost later in fibrotic bN. Loss of ADAMTS13 and accumulation of VWF in fibrotic but not hyalinotic arteriolar walls could further propagate fibrosis in bN.

• 出版日期2011-6