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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:25 |
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| Enthalten in: |
The journal of vascular access - 25(2024), 2 vom: 14. März, Seite 566-575 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Feng, Tao [VerfasserIn] |
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| Links: |
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| Themen: |
Arteriovenous fistula |
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| Anmerkungen: |
Date Completed 14.03.2024 Date Revised 14.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1177/11297298221124730 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347187048 |
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| 100 | 1 | |a Feng, Tao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pentoxifylline decreases the activity of the nucleotide-binding oligomerization domain-like receptor protein 3 pathway |b potential role for preventing arteriovenous fistula stenosis |
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| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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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