2. Academic Validation
  3. 3, 4-Benzopyrene (Bap) aggravated abdominal aortic aneurysm formation by targeting pyroptosis in smooth muscle cells through ET-1 mediated NLRP3-inflammasome activation

3, 4-Benzopyrene (Bap) aggravated abdominal aortic aneurysm formation by targeting pyroptosis in smooth muscle cells through ET-1 mediated NLRP3-inflammasome activation

  • Int Immunopharmacol. 2023 Aug 29;124(Pt A):110851. doi: 10.1016/j.intimp.2023.110851.
Shuai Liu 1,  Yang-Jing Xue 2,  Ri-Peng Yin 2,  Bo-Sen Wu 2,  Yong-Wei Yu 3,  Ying-Ying Zhou 4,  Jie Wang 5,  Kang-Ting Ji 6
Affiliations

Affiliations

  • 1 Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Cardiology, The First People's Hospital oF Jiashan, Jiaxing, Zhejiang 314100, China.
  • 2 Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 3 Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Critical Care Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
  • 4 Department of Endocrinology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 5 Department of Endocrinology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: 393551062@qq.com.
  • 6 Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China. Electronic address: jikt@wmu.edu.cn.
PMID: 37651853 DOI: 10.1016/j.intimp.2023.110851
Abstract

According to epidemiological studies, smoking is one of the leading causes of the high incidence of abdominal aortic aneurysms (AAA).3,4-Benzopyrene (Bap) is a by-product of coal tar and tobacco combustion produced by the incomplete combustion of organic fuels. It is an essential component of both automobile exhaust and tobacco smoke, it is also an important member of the air pollutants. However, the exact mechanism by which Bap can worsen the condition of patients with AAA and increase the mortality of patients with AAA remains unknown. This research aims to investigate the role of Bap in inducing Pyroptosis in AAA. In vitro experiments, we revealed that pyroptosis-Gasdermin D (GSDMD) increased when Bap was used. Additionally, the release of inflammatory factors, such as IL-1β and IL-18 were also rising. An mRNA Sequencing analysis revealed that macrophages expressed a high level of the endothelin gene when cells were stimulated by Bap. It seemed that smooth muscle cells Pyroptosis was related to macrophages. Experiments revealed that endothelin could increase the calcium ion concentration in smooth muscle cells, resulting in a large amount of ROS and activation of NLRP3 inflammasomes. We discovered that treatment with Endothelin Receptor antagonist (ABT-546) in vivo and calcium ion chelator (BAPTA) in vitro decreased AAA diameter, downregulated NLRP3 inflammasomes and ROS, and significantly reduced the number of activated GSDMD. Inflammatory mediators were released at a lower level. These findings suggest that Bap-induced Pyroptosis may be mediated by the ET-1-Ca2+-inflammasome pathway, providing a new way to reduce mortality in AAA patients.

Keywords

3, 4-Benzopyrene; Abdominal aortic aneurysm; Endothelin-1; Oxidative stress; Pyroptosis.

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