Dataset Information

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

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Xia J

PROVIDER: S-EPMC7723640 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Xia Jinggang J Zhang Jia J Chang Jing J Tian Yi Y Li Jubo J Zhang Baojie B Zeng Xiangjun X Yin Chunlin C

Annals of translational medicine 20201101 21

<h4>Background</h4>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.<h4>Methods</h4>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 patient ...[more]

PMID: 33313133

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Project description:ObjectiveThis study aimed to explore whether treatment with the glucagon-like peptide-1 (GLP-1) analog liraglutide reduces intimal hyperplasia after coronary stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic swine.MethodsFifteen pigs were divided into a diabetes mellitus (DM) group (n = 6), a DM + liraglutide treatment group (L group) (n = 6) and a sham group (n = 3). A total of 24 everolimus-eluting stents were implanted in the left anterior descending and right coronary arteries at 3 weeks. A novel continuous glucose monitoring system (GMS) was used for 2 weeks. The means and standard deviations (SDs) were measured and calculated by the GMS. At 22 weeks, the lumen area (LA), neointimal thickness (NIT), neointimal area (NIA), and percent area stenosis (%AS) were analyzed by optical coherence tomography. Plasma tumor necrosis factor-α, interleukin-6, and interleukin-10 were assayed by ELISA. The intima protein expression levels of NLRP3, interleukin-1β, interleukin-18 and interleukin-10 were examined using Western blot analysis. Histology was used to evaluate the healing response. In an in vitro study, THP-1 cells were divided into control, high glucose (HG), HG + liraglutide, and HG + liraglutide + Exe(9-39) (a GLP-1 receptor inhibitor) groups.ResultsThe L group had a lower SD, NIT, NIA, and %AS; a larger LA; reduced inflammation and injury scores; lower expression levels of tumor necrosis factor-α, interleukin-6, NLRP3, interleukin-1β, and interleukin-18; and higher expression of interleukin-10 compared with those of the DM group (p < 0.05). In the in vitro study, similar results were obtained in the HG + liraglutide group, and Exe(9-39) abolished the effect of liraglutide (p < 0.05).ConclusionsLiraglutide treatment reduces intimal hyperplasia after stent implantation via regulation of glycemic variability, the NLRP3 inflammasome, and IL-10 in diabetic pigs in a GLP-1 receptor-dependent manner. Reducing the inflammation induced by glycemic variability may be one of the cardioprotective mechanisms of liraglutide.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

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