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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2016 ; 310
(6
): F466-76
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A new model of an arteriovenous fistula in chronic kidney disease in the mouse:
beneficial effects of upregulated heme oxygenase-1
#MMPMID26672617
Kang L
; Grande JP
; Hillestad ML
; Croatt AJ
; Barry MA
; Katusic ZS
; Nath KA
Am J Physiol Renal Physiol
2016[Mar]; 310
(6
): F466-76
PMID26672617
show ga
The arteriovenous fistula (AVF) is the preferred hemodialysis vascular access,
but it is complicated by high failure rates and attendant morbidity. This study
provides the first description of a murine AVF model that recapitulates two
salient features of hemodialysis AVFs, namely, anastomosis of end-vein to
side-artery to create the AVF and the presence of chronic kidney disease (CKD).
CKD reduced AVF blood flow, observed as early as 3 days after AVF creation, and
increased neointimal hyperplasia, venous wall thickness, thrombus formation, and
vasculopathic gene expression in the AVF. These adverse effects of CKD could not
be ascribed to preexisting alterations in blood pressure or vascular reactivity
in this CKD model. In addition to vasculopathic genes, CKD induced potentially
vasoprotective genes in the AVF such as heme oxygenase-1 (HO-1) and HO-2. To
determine whether prior HO-1 upregulation may protect in this model, we
upregulated HO-1 by adeno-associated viral gene delivery, achieving marked venous
induction of the HO-1 protein and HO activity. Such HO-1 upregulation improved
AVF blood flow and decreased venous wall thickness in the AVF. Finally, we
demonstrate that the administration of carbon monoxide, a product of HO, acutely
increased AVF blood flow. This study thus demonstrates: 1) the feasibility of a
clinically relevant murine AVF model created in the presence of CKD and involving
an end-vein to side-artery anastomosis; 2) the exacerbatory effect of CKD on
clinically relevant features of this model; and 3) the beneficial effects in this
model conferred by HO-1 upregulation by adeno-associated viral gene delivery.