2. Academic Validation
  3. Oltipraz, the activator of nuclear factor erythroid 2-related factor 2 (Nrf2), protects against the formation of BAPN-induced aneurysms and dissection of the thoracic aorta in mice by inhibiting activation of the ROS-mediated NLRP3 inflammasome

Oltipraz, the activator of nuclear factor erythroid 2-related factor 2 (Nrf2), protects against the formation of BAPN-induced aneurysms and dissection of the thoracic aorta in mice by inhibiting activation of the ROS-mediated NLRP3 inflammasome

  • Eur J Pharmacol. 2022 Nov 3;175361. doi: 10.1016/j.ejphar.2022.175361.
Dashuai Wang 1,  Jia Wu 2,  Sheng Le 3,  Hongfei Wang 4,  Jingjing Luo 4,  Rui Li 4,  Xing Chen 4,  Song Yu 4,  Long Wu 4,  Ping Ye 5,  Xinling Du 6,  Xiaofan Huang 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan Province, China; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Road 1277, Wuhan, 430022, China.
  • 2 Key Laboratory for Molecular Diagnosis of Hubei Province, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, ShengLi Street 26, Wuhan, 430014, China.
  • 3 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Road 1277, Wuhan, 430022, China; Department of Thoracic Surgery (S.L.), Zhongnan Hospital of Wuhan University, Wuhan University, East Lake Road 169, Wuhan, 430072, China.
  • 4 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Road 1277, Wuhan, 430022, China.
  • 5 Key Laboratory for Molecular Diagnosis of Hubei Province, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, ShengLi Street 26, Wuhan, 430014, China; Department of Cardiology, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, ShengLi Street 26, Wuhan, 430014, China. Electronic address: blue314@163.com.
  • 6 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Road 1277, Wuhan, 430022, China. Electronic address: xinlingdu@hust.edu.cn.
  • 7 Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, JieFang Road 1277, Wuhan, 430022, China. Electronic address: dr_xfhuang@hust.edu.cn.
PMID: 36336010 DOI: 10.1016/j.ejphar.2022.175361
Abstract

Background: Thoracic aortic aneurysm and dissection (TAAD) is caused by the Apoptosis and phenotypic transformation of vascular smooth muscle cells (VSMCs). The dysfunction of VSMCs affects their secretion of chemokines such as monocyte chemoattractant protein-1 (MCP-1) to recruit the infiltration of macrophages which release proinflammatory cytokines and Matrix Metalloproteinases (MMPs) to accelerate the process of TAAD formation.

Approach and results: We analyzed the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) in aortic tissues of TAAD patients and the β-aminopropionitrile fumarate (BAPN)-induced mouse model, and the levels of Nrf2 were elevated in both aortic lesions. Treatment with the Nrf2 activator oltipraz protects against the formation of BAPN-induced aneurysm and dissection, as demonstrated by a higher survival rate, postponing the time of aortic rupture, and inhibiting aortic luminal dilation. In addition, the thoracic aortas of BAPN-treated mice inhibited the Apoptosis and phenotypic transformation of VSMCs. When treated with oltipraz, they had reduced macrophage infiltration proinflammatory cytokines and MMPs. Furthermore, oltipraz treatment promoted the translocation of Nrf2 and downregulated the NLRP3 pathway.

Conclusion: Nrf2 plays a crucial role in protecting against TAAD development, and persistent activation of Nrf2 is a promising therapeutic strategy against the progression of TAAD.

Keywords

Monocyte chemoattractant protein-1; NLRP3 inflammasome; Nuclear factor erythroid 2-related factor 2; Oltipraz; Thoracic aortic aneurysm and dissection; Vascular smooth muscle cells.

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