Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway

Haole Liu; Kangli Tian; Weilai Fu; Longlong Qin; Ruipu Tian; Panpan Wei; Jiawei Zou; Naqash Alam; Fizza Malik; Kexin Li; Meng Li; Boyu Xu; Jia Guo; Congcong Xia; Rong Wang; Weirong Wang; Liang Bai; Enqi Liu; Baohui Xu; Yankui Li; Sihai Zhao

doi:10.1016/j.jpha.2025.101453

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Article Navigation > Journal of Pharmaceutical Analysis > 2025 > Accepted Manu

Haole Liu, Kangli Tian, Weilai Fu, Longlong Qin, Ruipu Tian, Panpan Wei, Jiawei Zou, Naqash Alam, Fizza Malik, Kexin Li, Meng Li, Boyu Xu, Jia Guo, Congcong Xia, Rong Wang, Weirong Wang, Liang Bai, Enqi Liu, Baohui Xu, Yankui Li, Sihai Zhao. Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101453

Citation:

Haole Liu, Kangli Tian, Weilai Fu, Longlong Qin, Ruipu Tian, Panpan Wei, Jiawei Zou, Naqash Alam, Fizza Malik, Kexin Li, Meng Li, Boyu Xu, Jia Guo, Congcong Xia, Rong Wang, Weirong Wang, Liang Bai, Enqi Liu, Baohui Xu, Yankui Li, Sihai Zhao. Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101453

Citation:

Haole Liu, Kangli Tian, Weilai Fu, Longlong Qin, Ruipu Tian, Panpan Wei, Jiawei Zou, Naqash Alam, Fizza Malik, Kexin Li, Meng Li, Boyu Xu, Jia Guo, Congcong Xia, Rong Wang, Weirong Wang, Liang Bai, Enqi Liu, Baohui Xu, Yankui Li, Sihai Zhao. Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2025.101453

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Tranilast ameliorates experimental abdominal aortic aneurysm by inhibiting the NLRP3 inflammasome pathway

doi: 10.1016/j.jpha.2025.101453

a. Institute of Cardiovascular Science, Basic Medical School, Xi’an Jiaotong University, Xi’an 710061, China;
b. Department of Vascular Surgery, The Second Hospital of Tianjin Medical University, Tianjin 300211, China;
c. Laboratory Animal Center, Xi’an Jiaotong University Health Science Center, Xi’an 710061, China;
d. Department of Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA

Funds:

This work was funded by the Natural Science Foundation of Shaanxi Province (2023-CX-PT-17 to Sihai Zhao and 2022PT-41 to Congcong Xia), the Tianjin Science and Technology Project (No. 23JCZXJC00160 to Yankui Li), and the Natural Science Project of Xi’an Jiaotong University (YXJLRH2022073 to Sihai Zhao). We also thank Haiwen Hou for her kind help in assisting with the animal model.

Received Date: Apr. 08, 2025
Accepted Date: Sep. 16, 2025
Rev Recd Date: Aug. 10, 2025
Available Online: Sep. 19, 2025

Abstract

Abstract

An abnormal inflammatory response is one of the main pathogenic mechanisms of abdominal aortic aneurysms (AAAs), and tranilast, an antiallergic drug, has anti-inflammatory properties. The effect and mechanism of action of tranilast on AAAs remain incompletely defined. To evaluate the preventive and therapeutic effects on experimental AAAs induced by intra-aortic elastase infusion in mice, tranilast was administered either before or after elastase infusion and continued until the experimental endpoint. Bioinformatics analysis and corresponding validation experiments were used to explore the possible mechanisms by which tranilast affects AAA progression. Compared with vehicle treatment, both tranilast pre-treatment and post-treatment therapies markedly inhibited aneurysmal aortic expansion. Treatment with tranilast attenuated the degradation of aneurysmal medial elastin and the depletion of smooth muscle cells. Aortic leukocyte accumulation was significantly lower in aneurysmal aortas from tranilast-treated mice than in those from vehicle-treated mice. Mural abnormal angiogenesis and aortic matrix metalloproteinase (MMP) 2 and 9 expression levels were also reduced after tranilast treatment. Bioinformatics analysis revealed that nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) may be a hub target through which tranilast affects AAAs. NLRP3 expression levels were lower in the aneurysmal aortas of tranilast-treated mice than in those of vehicle-treated elastase-infused mice. Both Nlrp3 deficiency and treatment with the NLRP3 inhibitor MCC950 attenuated experimental AAAs. However, cotreatment with tranilast had no additive or synergistic influence on AAA suppression. Additionally, tranilast treatment reduced caspase 1 cleavage by the NLRP3 inflammasome and consequently interleukin-1β secretion in peritoneal macrophages in vitro. These findings indicate that the protective effect of tranilast on AAA may be partially mediated by the inhibition of the NLRP3 inflammasome pathway and may represent a potential drug for the treatment of AAA in the clinic.
- Abdominal aortic aneurysm,
- NLRP3,
- inflammation,
- tranilast,
- macrophages,
- angiogenesis,
- matrix metalloproteinase,
- therapy

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References(49)

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