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

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