1. Academic Validation
  2. Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation

Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation

  • Aging (Albany NY). 2020 Apr 14;12(7):6415-6435. doi: 10.18632/aging.103038.
Lin Cong 1 Ziyu Gao 1 Yinghong Zheng 1 Ting Ye 1 Zitong Wang 1 Pengyu Wang 1 Manman Li 1 Bowen Dong 1 Wei Yang 1 Quanfeng Li 1 Shupei Qiao 2 Cao Wang 2 Yijun Shen 2 Hong Li 1 Weiming Tian 2 Liming Yang 1 3
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China.
  • 2 School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China.
  • 3 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing 100037, China.
Abstract

The incidence of atherosclerosis (AS), a major contributor to Cardiovascular Disease, is steadily rising along with an increasingly older population worldwide. Pyroptosis, a form of inflammatory programmed cell death, determines the release of pro-inflammatory mediators by endothelial cells, smooth muscle cells, and atheroma-associated macrophages and foam cells, thereby playing a critical role in AS progression. Canonical Pyroptosis is mediated by inflammasome formation, activation of Caspase-1, and maturation and release of proinflammatory cytokines. Electrical stimulation (ES) is a noninvasive, safe therapy that has been shown to alleviate symptoms in several health conditions. Here, we investigated the anti-inflammatory and anti-pyroptotic effects of ES in human THP-1 macrophages treated with the Dipeptidyl Peptidase Inhibitor Val-boroPro (VbP). We found that ES downregulated NOD-like receptor family protein 3 (NLRP3) inflammasome, ASC, and Caspase-1 expression and abrogated the release of Interleukin-1β (IL-1β) and Interleukin-18 (IL-18), indicating effective Pyroptosis inhibition. These changes were paralleled by a reduction in Reactive Oxygen Species (ROS) production, reversal of VbP-induced sirtuin3 (SIRT3) downregulation, deacetylation of ATG5, and induction of Autophagy. These findings suggest that ES may be a viable strategy to counteract pyroptosis-mediated inflammation in AS by raising SIRT3 to promote Autophagy and inhibit ROS generation.

Keywords

ROS; electrical stimulation; macrophages; pyroptosis; sirtuin3.

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