Abstract

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.

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Publisher Full Text

Authors

Bockmeyer CL, Forstmeier V, Modde F, Lovric S, Claus RA, Schiffer M, Agustian PA, Grothusen C, Grote K, Birschmann I, Theophile K, Kreipe HH, Bröcker V, Becker JU

Institution

Institute of Pathology, Hannover Medical School, Hannover, Lower Saxony, Germany.

Source

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 26:6 2011 Jun pg 1871-81

MeSH

ADAM Proteins
Arteries
Biological Markers
Case-Control Studies
Humans
Immunoenzyme Techniques
Integrin beta3
Muscle Contraction
Myocytes, Smooth Muscle
Nephrosclerosis
Prognosis
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
von Willebrand Factor

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

20923926