Open AccessTLR-4 Inhibition Attenuates Inflammation, Thrombosis, and Stenosis in Arteriovenous Fistula in Yucatan Miniswine
Author(s) -
Vikrant Rai,
Mohamed M. Radwan,
Sunil Nooti,
Finosh G. Thankam,
Harbinder Singh,
Devendra K. Agrawal
Publication year - 2022
Publication title -
cardiology and cardiovascular medicine
Language(s) - English
Resource type - Journals
ISSN - 2572-9292
DOI - 10.26502/fccm.92920280
Subject(s) - medicine , arteriovenous fistula , thrombosis , inflammation , stenosis , cardiology , radiology
Arteriovenous fistula (AVF) is the preferred vascular access in hemodialysis patients; however, it is afflicted with a high failure rate. Chronic inflammation, excessive neointimal hyperplasia (NIH), vessel stenosis, early thrombosis, and failure of outward remodeling are the major causes of AVF maturation failure. Inflammatory mediator toll-like receptor (TLR)-4 plays a critical role in NIH, arterial thrombosis, and stenosis. We investigated the effect of TLR-4 inhibition on early thrombosis. Yucatan miniswine were used to create AVF involving femoral artery and femoral vein and treated with TLR-4 inhibitor TAK-242 with ethanol as the vehicle. The vessels were assessed after 12 weeks using histomorphometry, immunostaining, ultrasound, angiography, and optical coherence tomography. Inhibition of TLR-4 attenuated inflammation and early thrombosis in 50% of animals, and blood flow was present through AVF in 25% of animals. Thus, targeting TLR-4 to attenuate inflammation and early thrombosis might be a therapeutic approach to keep AVF patent and maintain blood flow through the outflow vein.