PMID- 32289749 OWN - NLM STAT- MEDLINE DCOM- 20210225 LR - 20210225 IS - 1945-4589 (Electronic) IS - 1945-4589 (Linking) VI - 12 IP - 7 DP - 2020 Apr 14 TI - Electrical stimulation inhibits Val-boroPro-induced pyroptosis in THP-1 macrophages via sirtuin3 activation to promote autophagy and inhibit ROS generation. PG - 6415-6435 LID - 10.18632/aging.103038 [doi] AB - 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-1beta (IL-1beta) 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. FAU - Cong, Lin AU - Cong L AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Gao, Ziyu AU - Gao Z AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Zheng, Yinghong AU - Zheng Y AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Ye, Ting AU - Ye T AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Wang, Zitong AU - Wang Z AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Wang, Pengyu AU - Wang P AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Li, Manman AU - Li M AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Dong, Bowen AU - Dong B AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Yang, Wei AU - Yang W AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Li, Quanfeng AU - Li Q AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Qiao, Shupei AU - Qiao S AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China. FAU - Wang, Cao AU - Wang C AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China. FAU - Shen, Yijun AU - Shen Y AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China. FAU - Li, Hong AU - Li H AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. FAU - Tian, Weiming AU - Tian W AD - School of Life Science and Technology, Harbin Institute of Technology, Harbin 150006, China. FAU - Yang, Liming AU - Yang L AD - Department of Pathophysiology, Basic Medical Science, Harbin Medical University, Harbin 150081, China. AD - State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Beijing 100037, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200414 PL - United States TA - Aging (Albany NY) JT - Aging JID - 101508617 RN - 0 (Boronic Acids) RN - 0 (Dipeptides) RN - 0 (Inflammasomes) RN - 0 (Interleukin-1beta) RN - 0 (NLR Family, Pyrin Domain-Containing 3 Protein) RN - 0 (NLRP3 protein, human) RN - 0 (PT-100 dipeptide) RN - 0 (Reactive Oxygen Species) RN - EC 3.4.14.- (Dipeptidyl-Peptidases and Tripeptidyl-Peptidases) RN - EC 3.4.22.36 (Caspase 1) RN - EC 3.5.1.- (Sirtuin 3) SB - IM MH - *Atherosclerosis/immunology/metabolism MH - Boronic Acids/pharmacology MH - Caspase 1/metabolism MH - Dipeptides/pharmacology MH - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/*antagonists & inhibitors MH - Electric Stimulation/*methods MH - Humans MH - Inflammasomes/*metabolism MH - Interleukin-1beta/metabolism MH - *Macrophages/immunology/metabolism MH - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism MH - Pyroptosis/drug effects/physiology MH - Reactive Oxygen Species/metabolism MH - Sirtuin 3/*metabolism MH - THP-1 Cells PMC - PMC7185124 OTO - NOTNLM OT - ROS OT - electrical stimulation OT - macrophages OT - pyroptosis OT - sirtuin3 COIS- CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest. EDAT- 2020/04/15 06:00 MHDA- 2021/02/26 06:00 PMCR- 2020/04/15 CRDT- 2020/04/15 06:00 PHST- 2020/01/09 00:00 [received] PHST- 2020/03/04 00:00 [accepted] PHST- 2020/04/15 06:00 [pubmed] PHST- 2021/02/26 06:00 [medline] PHST- 2020/04/15 06:00 [entrez] PHST- 2020/04/15 00:00 [pmc-release] AID - 103038 [pii] AID - 10.18632/aging.103038 [doi] PST - ppublish SO - Aging (Albany NY). 2020 Apr 14;12(7):6415-6435. doi: 10.18632/aging.103038. Epub 2020 Apr 14.