Adenovirus-Mediated Expression of β-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs

Abstract

Background-Hemodialysis

Letter Regarding Article by Luo et al, “Adenovirus-Mediated Expression of β-Adrenergic Receptor Kinase C-Terminus Reduces Intimal Hyperplasia and Luminal Stenosis of Arteriovenous Polytetrafluoroethylene Grafts in Pigs”

“…1 Compared with their earlier report, the patency rate 4 weeks after the construction of the arteriovenous ePTFE grafts was much lower in our study. 2 They suggest that the longer length of our ePTFE grafts and slower blood flow contributed to the lower patency rate.…”

“…We reasoned that the different structure and resultant flow velocity may have contributed to the discrepancy in patency rate. 1 They also speculate that thrombotic lesions might have accelerated graft failure in our study. Our study was not designed to examine the relative contribution of early thrombosis and gradual intimal hyperplasia to graft failure in the absence of an antiplatelet regimen.…”

Animal models for the assessment of novel vascular conduits

“…This problem has long been recognized clinically in humans where the known stimuli at the distal anastomosis of compliance mismatch, turbulent flow, and altered wall shear stress are exaggerated by the presence of high flow through the conduit (typically 1.0-1.5 L/min) as well as repetitive puncture resulting in ongoing endothelial injury, platelet activation, and myointimal proliferation. 127 Therapeutic strategies attempting to reduce IH affecting carotid artery-jugular vein ePTFE grafts in swine include transduction of the venous limb to reduce smooth muscle cell (SMC) proliferation 128 and coating ePTFE grafts with anti-CD34 antibodies intended to capture circulating endothelial progenitor cells. 129 Roy-Chaudhury et al 130 placed ePTFE conduits as femoral arteriovenous grafts in pigs, showing almost complete abolition of luminal stenosis by wrapping the graft-vein anastomosis with a paclitaxel-loaded wrap.…”

Novel Therapies for Hemodialysis Vascular Access Dysfunction

“…However, neointimal hyperplasia was markedly increased in the pl-eNOStransfected AVFs, possibly because extraordinarily high levels of eNOS expression resulted in the production of excessive amounts of reactive nitrogen species and oxidative stress. The gene for b-adrenergic receptor kinase C terminus has been delivered to the jugular vein segment of AVG in swine (62). Significant inhibition of neointimal hyperplasia at the veingraft anastomosis at 4 weeks occurred compared with mocktransfected AVG.…”