Pentoxifylline decreases the activity of the nucleotide-binding oligomerization domain-like receptor protein 3 pathway: potential role for preventing arteriovenous fistula stenosis.

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)-1β 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 AVF + 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 AVF models, the AVF + uraemia models had much higher expressions of NLRP3, caspase-1, IL-1β 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.