Pentoxifylline decreases the activity of the nucleotide-binding oligomerization domain-like receptor protein 3 pathway: potential role for preventing arteriovenous fistula stenosis
JOURNAL OF VASCULAR ACCESS(2024)
Abstract
Purpose: This study aimed to determine the effect of pentoxifylline (PTX) on the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway and its role in preventing arteriovenous fistula (AVF) failure. Methods: Vein samples were collected from AVF failure patients and from patients who underwent surgical AVF as a control. The expressions of CD34 and NLRP3 in AVF tissues were detected by immunohistochemistry and Western blotting. Arteriovenous fistula rat models were established by the end-to-end anastomosis of the common carotid artery and external jugular vein. The AVF models were divided into the following groups: AVF, AVF + PTX, AVF + uraemia and AVF + uraemia + PTX. Six weeks after surgery, the AVF tissues in each group were collected to detect the expressions of CD34, NLRP3, caspase-1 and interleukin (IL)-1 beta by immunohistochemistry, Western blotting and real-time polymerase chain reaction. Results: The expressions of NLRP3 and CD34 in human AVF failure tissues were significantly higher than those in normal veins (p < 0.001), indicating that NLRP3 was upregulated in patients with AVF failure. In our animal study, the veins in the AVE + uraemia group exhibited heavy hyperplasia, and the boundary between the media and the adventitia was not clear. However, PTX alleviated this hyperplasia. Compared with the AVE models, the AVE + uraemia models had much higher expressions of NLRP3, caspase-1, IL-1 beta and CD34 (p < 0.001). However, PTX had the opposite effect against uraemia on the NLRP3 inflammasome pathway at both the gene and protein levels. Conclusions: Our findings provide new insights that show that PTX can decrease the activity of the NLRP3 inflammasome pathway in AVF models. Pentoxifylline has the potential as a drug for preventing intimal hyperplasia and AVF failure.
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Key words
Arteriovenous fistula,pentoxifylline,NLRP3,caspase-1,IL-1 beta
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