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The effects of glycaemic variability on intimal hyperplasia and plaque stability after stenting via autophagy-mediated G3BP1/NLRP3 inflammasome.

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机构: [1]Department of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China [2]Department of Physiology and Pathophysiology, Capital Medical University, Beijing, China [3]Department of Pathology, Beijing Youan Hospital, Capital Medical University, Beijing, China [4]Beijing Anzhen Hospital, Capital Medical University, Beijing, China [5]Department of Animal Experimental Center, Fuwai Hospital, National Center for Cardiovascular Disease, China Academy of Medical Sciences, Beijing, China
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关键词: Glycaemic variability (GV) diabetes coronary heart disease (CHD) intima plaque stability autophagy G3BP1 NLRP3 inflammasome

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The objective of this study was to investigate the effects of glycaemic variability (GV) on intimal hyperplasia and plaque stability after coronary stenting via autophagy-mediated G3BP1/NLRP3 inflammasome signalling. In the clinical study, between July 2017 and December 2017, 95 patients with acute myocardial infarction (AMI) and diabetes mellitus (DM) comorbidity received stent implantation. The patients were followed up for 2 years after discharge. The patients were divided into a low-GV (n=61) and high-GV (n=34) group, and the incidence of recurrent AMI was measured. In the animal study, thirteen pigs were divided into a sham (n=3), low-GV DM (n=5) and high-GV DM group (n=5). Intima samples were analysed by optical coherence tomography 22 weeks after coronary stenting. Becn1, LC3B, p62, G3BP1 and NLRP3 protein levels in the intima were examined by western blot. In vitro experiments with THP-1 cells were also conducted. In the high-GV group, patients exhibited a higher recurrent AMI, greater neointimal thickness, increased p62 and NLRP3 expression, and decreased Becn1, LC3B and G3BP1 expression compared with the low-GV group (P<0.05). The effects of high GV could be abolished by rapamycin but were aggravated by 3-methyladenine. GV might impact the intimal hyperplasia and plaque stability via autophagy-mediated G3BP1/NLRP3 inflammasome signalling. GV and the autophagy-mediated G3BP1/NLRP3 inflammasome may be promising targets for the treatment of coronary heart disease. 2020 Annals of Translational Medicine. All rights reserved.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 2 区 肿瘤学
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第一作者机构: [1]Department of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
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通讯机构: [*1]Department of Physiology and Pathophysiology, Capital Medical University, Beijing China. [*2]Department of Cardiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Diseases, Beijing, China
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