Pentraxin 3 and complement cascade activation in the failure of arteriovenous fistula.
OBJECTIVE
Pentraxin-3 (PTX3) has been suggested to play a role in the development of vascular pathology. Stenosis of arteriovenous fistula (AVF) leading to its failure is the major cause of morbidity in hemodialysis patients. To date, little is known on the pathogenesis of AVF stenosis. The aim of the present study was to investigate the potential role of PTX3 in this setting.


RESULTS
A sample of venous wall was collected at the time of AVF formation in 44 patients with end stage renal disease. Ten patients developed AVF stenosis and from these patients a second portion of the venous wall was obtained during surgical revision of the AVF. Confocal laser scanning microscopy demonstrated that PTX3 immunostaining, hardly detectable in native AVF, was significantly increased in failed AVF, showing a specific co-localization with endothelial cell markers. Circulating mononuclear cells isolated at the time of AVF revision presented a significantly higher PTX3 mRNA expression than those collected during AVF creation. Interestingly, a significant deposition of C5b-9 on endothelial cells, co-localizing with PTX3, was observed in stenotic AVF.


CONCLUSIONS
The present study demonstrates for the first time a close association between PTX3 deposition and complement activation at the endothelial cell level in failed AVF and suggests a role for PTX3 in modulating innate immunity in the pathogenesis of AVF stenosis.
Castellano
Giuseppe
G
Renal, Dialysis and Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, Policlinico, Piazza G. Cesare 11, Bari, Italy. g.castellano@nephro.uniba.it
Di Vittorio
Angela
A
Dalfino
Giuseppe
G
Loverre
Antonia
A
Marrone
Daniela
D
Simone
Simona
S
Schena
Francesco Paolo
FP
Pertosa
Giovanni
G
Grandaliano
Giuseppe
G
D000328:Adult; D000368:Aged; D001163:Arteriovenous Anastomosis / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D003167:Complement Activation; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D003251:Constriction, Pathologic / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D006435:Renal Dialysis; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D017211:Treatment Failure; D000099153:Pentraxins
D015415:Biomarkers; D002097:C-Reactive Protein; D015938:Complement Membrane Attack Complex; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D000099153:Pentraxins