Over-expression of IGF-related peptides in stenoses of native arteriovenous fistulas in hemodialysis patients.
BACKGROUND
Insulin-like growth factors (IGFs) are known to play an important role in atherogenesis. The aim of our study was to assess the local expression of IGF-related peptides in stenosed hemodialysis fistulas and compare these with their respective serum levels.


METHODS
We investigated 15 stenosed vein segments of primary arteriovenous fistulas, 29 non-stenosed control vein segments from uremic patients and 15 non-stenosed control saphenous vein segments. Immunohistochemistry was performed for IGF-I, insulin, IGF-binding proteins (IGFBPs)-1, -2, -3 and -4, the acid labile subunit (ALS) and type 1 IGF-receptor (IGF-R). Serum levels were measured by specific radioimmunoassays.


RESULTS
Compared to both control groups, a significantly higher expression of the following IGF-related peptides was seen in the stenotic (neo)intima: IGF-I, IGFBP-1, -2, -3, -4 and IGF-R; in the stenotic media: IGF-I and IGFBP-3 and in the endothelium of stenotic fistulas: IGF-I (all p<0.05). Staining against ALS and insulin was negative in all vessels. Serum IGF-I levels did not differ. Serum levels of IGFBP-1, -2, -3 and -4 were significantly higher in patients with renal disease (all p<0.05). There were no correlations between local and systemic IGF-related peptide levels. There were correlations of neointimal expression of IGF-I, IGFBP-1, -2, -3, -4 and IGF-R with both hypercellularity and the presence of inflammatory cells (p<0.05).


CONCLUSIONS
In the stenotic arteriovenous fistula of hemodialysis patients, expression of the peptides IGF-I, IGFBP-1, -2, -3, -4 and IGF-R was significantly increased and showed a positive correlation with neointimal inflammation and hypercellularity (all p<0.05). IGF-related peptides are most likely synthesized locally and might be involved in the initiation and/or progression of neointimal thickening of primary arteriovenous fistulas.
Stracke
Sylvia
S
Department of Internal Medicine I, Division of Nephrology, University of Ulm, Germany. sylvia.stracke@medizin.uni-ulm.de
Konner
Klaus
K
Köstlin
Isabella
I
Schneider
Markus
M
Herzog
Rosa
R
Jehle
Peter M
PM
Keller
Frieder
F
Friedl
Reinhard
R
D000368:Aged; D001166:Arteriovenous Shunt, Surgical; D002352:Carrier Proteins / Q000235:genetics; D003251:Constriction, Pathologic / Q000097:blood / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000473:pathology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D017526:Receptor, IGF Type 1 / Q000235:genetics*; D006435:Renal Dialysis / Q000009:adverse effects*; D017211:Treatment Failure; D015854:Up-Regulation; D014511:Uremia / Q000235:genetics / Q000473:pathology
D002352:Carrier Proteins; D006023:Glycoproteins; D018969:Insulin-Like Growth Factor Binding Proteins; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1