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

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.