PMID- 29673854 OWN - NLM STAT- MEDLINE DCOM- 20181211 LR - 20201209 IS - 1874-1754 (Electronic) IS - 0167-5273 (Linking) VI - 263 DP - 2018 Jul 15 TI - Silencing of Non-POU-domain-containing octamer-binding protein stabilizes atherosclerotic plaque in apolipoprotein E-knockout mice via NF-kappaB signaling pathway. PG - 96-103 LID - S0167-5273(18)30110-4 [pii] LID - 10.1016/j.ijcard.2018.04.018 [doi] AB - BACKGROUND: It remains unknown whether Non-POU-domain-containing octamer-binding protein (NonO) plays a causative role in plaque destabilization. We hypothesized that NonO gene silencing may stabilize atherosclerotic plaque by increasing P4Halpha1 expression and inhibiting the inflammation. METHODS AND RESULTS: Vulnerable atherosclerotic plaques were induced in ApoE-/- mice by high fat diet, perivascular collar placement and mental stress. Compared with normal carotid arteries, those contained vulnerable plaques had high NonO expression. In another in vivo experiment, mice contained vulnerable plaques were randomly divided into 5 groups to receive physiological saline, si-N.C-lentivirus (LV), si-NonO-LV, pGC-GFP-LV and NonO-LV, respectively. NonO overexpression increased while NonO silencing decreased the incidence of carotid plaque disruption. NonO overexpression enhanced macrophage infiltration and lipid deposition but reduced the content of vascular smooth muscle cells and collagen in plaques, leading to an increased plaque vulnerability index, whereas NonO silencing exhibited the opposite effect. In addition, NonO overexpression increased the expression of proinflammatory cytokines and matrix metalloproteinases and decreased the expression of P4Halpha1 both in vivo and in vitro, whereas NonO silencing showed the contrary effect. NonO co-immunoprecipitated with NF-kappaB p65, and promoted its nuclear translocation and phosphorylation, and these effects were reversed by NonO silencing. CONCLUSION: NonO may promote plaque destabilization and increase the incidence of plaque disruption in ApoE-/- mice by inducing the expression of inflammatory cytokines and matrix metalloproteinases and suppressing that of P4Halpha1. The mechanism may involve the interaction of NonO with NF-kappaB leading to enhanced NF-kappaB nuclear translocation and phosphorylation. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zhang, Kai AU - Zhang K AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. FAU - Zhang, Fang AU - Zhang F AD - Department of Pharmacy, Jinan Central Hospital Affiliated to Shandong University, Jinan, China. FAU - Yang, Jian-Min AU - Yang JM AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. FAU - Kong, Jing AU - Kong J AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. FAU - Meng, Xiao AU - Meng X AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. FAU - Zhang, Meng AU - Zhang M AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. FAU - Zhang, Cheng AU - Zhang C AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: zhangc@sdu.edu.cn. FAU - Zhang, Yun AU - Zhang Y AD - The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China. Electronic address: zhangyun@sdu.edu.cn. LA - eng PT - Journal Article DEP - 20180407 PL - Netherlands TA - Int J Cardiol JT - International journal of cardiology JID - 8200291 RN - 0 (Apolipoproteins E) RN - 0 (Cytokines) RN - 0 (DNA-Binding Proteins) RN - 0 (NF-kappa B) RN - 0 (Nono protein, mouse) RN - 0 (RNA-Binding Proteins) SB - IM MH - Animals MH - Apolipoproteins E/*deficiency/genetics MH - Cytokines/biosynthesis/genetics MH - DNA-Binding Proteins/antagonists & inhibitors/*biosynthesis/genetics MH - Gene Silencing/*physiology MH - Male MH - Mice MH - Mice, Knockout MH - NF-kappa B/genetics/*metabolism MH - Plaque, Atherosclerotic/genetics/*metabolism/pathology MH - RAW 264.7 Cells MH - RNA-Binding Proteins MH - Signal Transduction/*physiology OTO - NOTNLM OT - Atherosclerosis OT - Gene therapy OT - Inflammation OT - Non-POU-domain-containing octamer-binding protein OT - Plaque instability EDAT- 2018/04/21 06:00 MHDA- 2018/12/12 06:00 CRDT- 2018/04/21 06:00 PHST- 2018/01/07 00:00 [received] PHST- 2018/03/25 00:00 [revised] PHST- 2018/04/05 00:00 [accepted] PHST- 2018/04/21 06:00 [pubmed] PHST- 2018/12/12 06:00 [medline] PHST- 2018/04/21 06:00 [entrez] AID - S0167-5273(18)30110-4 [pii] AID - 10.1016/j.ijcard.2018.04.018 [doi] PST - ppublish SO - Int J Cardiol. 2018 Jul 15;263:96-103. doi: 10.1016/j.ijcard.2018.04.018. Epub 2018 Apr 7.