Melatonin attenuates high glucose‑induced endothelial cell pyroptosis by activating the Nrf2 pathway to inhibit NLRP3 inflammasome activation

Wang,Xuebin; Wang,Wei; Zhang,Rui; Ma,Baitao; Ni,Leng; Feng,Hai; Liu,Changwei

doi:10.3892/mmr.2023.12958

Melatonin attenuates high glucose‑induced endothelial cell pyroptosis by activating the Nrf2 pathway to inhibit NLRP3 inflammasome activation

Authors:
- Xuebin Wang
- Wei Wang
- Rui Zhang
- Baitao Ma
- Leng Ni
- Hai Feng
- Changwei Liu
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Affiliations: Department of Vascular Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, P.R. China, Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P.R. China, Department of Endovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450000, P.R. China
Published online on: February 10, 2023 https://doi.org/10.3892/mmr.2023.12958
Article Number: 71
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endothelial injury induced by hyperglycemia is the most critical initial step in the development of diabetic vasculopathy. The aim of this present study was to explore the prevention and treatment strategies and elucidate the specific mechanism of diabetes‑induced vascular endothelial injury. Melatonin, a hormone secreted by the pineal gland to regulate biological rhythm, serves an important role in maintaining human physiological function. Pyroptosis is a type of newly discovered inflammatory cell death. The current study first found by western blotting that melatonin could activate nuclear factor erythroid 2‑related factor 2 (Nrf2) pathway in human umbilical vein endothelial cells (HUVECs) under high glucose (HG) condition. Second, it found that pretreatment with Luzindole, a specific inhibitor of melatonin receptor (MT1/MT2), significantly reduced the activation of Nrf2 pathway by melatonin in HUVECs. It also found that pretreatment with melatonin or a specific NOD‑like receptor family, pyrin domain‑containing 3 (NLRP3) inhibitor (MCC950) pretreatment reduced HG‑induced endothelial cell pyroptosis. Finally, it was found that the protective effect of melatonin against reactive oxygen species/NLRP3 inflammasome pathway activation induced by HG in HUVECs was decreased after Nrf2 knockdown. In conclusion, the present study showed that melatonin may serve a protective role in HG‑induced vascular endothelial cell pyroptosis by activating the Nrf2 pathway to inhibit NLRP3 inflammasome activation. In addition, it was further found that melatonin attenuated HG‑induced vascular endothelial cell injury by interacting with its receptors (MT1/MT2) to promote activation of Nrf2 pathway.

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