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  2. Interleukin-37 ameliorates atherosclerosis by regulating autophagy-mediated endothelial cell apoptosis and inflammation

Interleukin-37 ameliorates atherosclerosis by regulating autophagy-mediated endothelial cell apoptosis and inflammation

  • Int Immunopharmacol. 2023 Apr 4;118:110098. doi: 10.1016/j.intimp.2023.110098.
Shengyang Xiao 1 Xiaoning Song 1 Man Zheng 1 Xinran Cao 1 Guo Ai 2 Baona Li 2 Gang Zhao 3 Haitao Yuan 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.
  • 2 Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China.
  • 3 Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China. Electronic address: zhaogang7181@sdfmu.edu.cn.
  • 4 Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China; Department of Cardiology, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, China. Electronic address: yuanhaitao@sdfmu.edu.cn.
Abstract

Atherosclerosis is a lipid-driven chronic inflammatory disease. Endothelial dysfunction is the initiating factor of atherosclerosis. Although much work has been done on the antiatherosclerotic effects of interleukin-37 (IL-37), the exact mechanism is still not fully understood. The aim of this study was to investigate whether IL-37 attenuates atherosclerosis by protecting endothelial cells and to confirm whether Autophagy plays a role in this effect. In apolipoprotein E knockout (ApoE-/-) mice fed with a high fat diet, IL-37 treatment significantly attenuated progression of atherosclerotic plaques, reduced endothelial cell Apoptosis and inflammasome activation. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an endothelial dysfunction model. We observed that IL-37 alleviated ox-LDL-induced endothelial cell inflammation and dysfunction, as evidenced by decreased nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation, ROS production, Apoptosis rate and secretion of inflammatory cytokines IL-1β and TNF-α. Furthermore, IL-37 could activate Autophagy in endothelial cells, which is characterized by the upregulation of LC3II/LC3I, the downregulation of p62 and an increase in autophagosomes. The Autophagy Inhibitor 3-Methyladenine (3-MA) dramatically reversed the promotion of Autophagy and the protective effect of IL-37 against endothelial injury. Our data illustrate that IL-37 alleviated inflammation and Apoptosis of atherosclerotic endothelial cells by enhancing Autophagy. The current study provides new insights and promising therapeutic strategies for atherosclerosis.

Keywords

Apoptosis; Atherosclerosis; Autophagy; Endothelial dysfunction; Interleukin-37; NLRP3.

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