Research Paper Volume 12, Issue 7 pp 6415—6435
Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation
- 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
received: January 9, 2020 ; accepted: March 4, 2020 ; published: April 14, 2020 ;https://doi.org/10.18632/aging.103038
How to Cite
Copyright © 2020 Cong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
AS: Atherosclerosis; VbP: Val-boroPro; ROS: reactive oxygen species; NAC: N-acetylcysteine; ES: Electrical stimulation; NLRP3: NOD-like receptor family protein 3; NLRP1: NOD-like receptor family protein 1; IL-1β: maturation of Interleukin-1β; IL-18: Interleukin-18; Sirt3: sirtuin3; CVD: cardiovascular disease; DCFH-DA: 2-7-Dichlorofluorescin diacetate; Rapa: rapamycin; 4-HNE: 4-hydroxynonenal; ELISA: Enzyme linked immunosorbent assay; RT-qPCR: Reverse transcription quantitative PCR; siRNA: Small interfering RNA; 3-MA: 3-methyladenine; TEM: Transmission electron microscopy; AO: acridine orange; AVOs: acidic vesicle organelles; MDC: monodansylcadaverine; ATG5: autophagy-related 5; LC3: microtubules associated protein 1 light chain 3-β.