Hypermethylation of the Micro-RNA 145 Promoter Is the Key Regulator for NLRP3 Inflammasome-Induced Activation and Plaque Formation

Wei Zhong; Bo Li; Yao Xu; Ping Yang; Rui Chen; Zhongqun Wang; Chen Shao; Juan Song; Jinchuan Yan

doi:10.1016/j.jacbts.2018.06.004

Hypermethylation of the Micro-RNA 145 Promoter Is the Key Regulator for NLRP3 Inflammasome-Induced Activation and Plaque Formation

JACC Basic Transl Sci. 2018 Sep 19;3(5):604-624. doi: 10.1016/j.jacbts.2018.06.004. eCollection 2018 Oct.

Authors

Wei Zhong¹, Bo Li¹, Yao Xu¹, Ping Yang¹, Rui Chen¹, Zhongqun Wang¹, Chen Shao¹, Juan Song¹, Jinchuan Yan¹

Affiliation

¹ Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, China.

Abstract

Two major issues are involved in clinical atherosclerosis treatment. First, there are no significant clinical markers for early diagnosis of atherosclerosis. Second, the plaque will not regress once it initiates even if the risk factors are removed. In this paper, the research shows that the hypermethylation level of the microRNA 145 (miR-145) promoter is related to a DNMT1 and TET2 dynamic imbalance. The reduction of miR-145 causes NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3) inflammasome activation through CD137/NFATc1 signaling. These findings could be a potential target for plaque regression in the future.

Keywords: 5-aza, 5-aza-2ʹ-deoxycytidine; 5-hmC, 5-hydroxymethylcytosine; ApoE, apolipoprotein E; BSP, bisulfite genomic sequencing; CVD, cardiovascular disease; ChIP, chromatin immunoprecipitation; DNA, deoxyribonucleic acid; DNMT, deoxyribonucleic acid methyltransferase; IL, interleukin; MSP, methylation-specific polymerase chain reaction; NFATc1, nuclear factor of activated T cells 1; RNA, ribonucleic acid; SMA, smooth muscle actin; TET, ten-eleven translocation; TNF, tumor necrosis factor; TNFRSF9; UTR, untranslated region; VSMC; VSMC, vascular smooth muscle cell; WT, wild type; atherosclerosis; cDNA, complementary deoxyribonucleic acid; inflammasome; mRNA, messenger ribonucleic acid; methylation; miR-145, microRNA 145; miRNA.