A GLP-1 Analog Liraglutide Reduces Intimal Hyperplasia After Coronary Stent Implantation via Regulation of Glycemic Variability and NLRP3 Inflammasome/IL-10 Signaling in Diabetic Swine

Abstract

Objective: This 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. Methods: Fifteen 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-a, interleukin-6, and interleukin-10 were assayed by ELISA. The intima protein expression levels of NLRP3, interleukin-1b, 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. Results: The 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-a, interleukin-6, NLRP3, interleukin-1b, and interleukin-18; and higher expression of interleukin-10 compared with those of the DM group (p < 0.05). In the in vitro study,

Activation of macrophage TBK1‐HIF‐1α‐mediated IL‐17/IL‐10 signaling by hyperglycemia aggravates the complexity of coronary atherosclerosis: An in vivo and in vitro study

“…In recent years, increased attention has been given to the role of aerobic glycolysis in atherosclerosis, especially the promotion of atherosclerosis occurrence and development by diabetes 15,16 . Our team's recent human clinical, animal, and cell studies showed that aerobic glycolysis‐related metabolic inflammation plays an important role in diabetes‐induced atherosclerosis 2,17 . However, the regulatory mechanism of glycolysis is not clear.…”

“…15,16 Our team's recent human clinical, animal, and cell studies showed that aerobic glycolysis-related metabolic inflammation plays an important role in diabetes-induced atherosclerosis. 2,17 However, the regulatory mechanism of glycolysis is not clear. Our study further confirmed the role of Warburg effect-related inflammation on the complexity of coronary atherosclerosis.…”

Activation of microglial GLP-1R in the trigeminal nucleus caudalis suppresses central sensitization of chronic migraine after recurrent nitroglycerin stimulation

“…Cells were incubated with serum-free media for 24 h prior to each experiment and seeded at 1 × 10 6 cells/dish in 100 mm culture dishes for western blotting and 3 × 10 4 cells/well in 24-well-culture plates for immunofluorescence. To study the role of GLP-1R in microglial inflammation, BV-2 cells were preincubated with the selective GLP-1R agonist liraglutide (100 nM, Selleck, TX, USA) and the antagonist exendin(9-39) (200 nM, MCE, USA) for 24 h, followed by LPS (1 µg/ml, Sigma-Aldrich, MO, USA) stimulation for 24 h. The doses of these drugs used with cells were based on previous data [34][35][36].…”

Clinical Efficacy and Mechanisms of Actions of the Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and High Risk of Cardiovascular Diseases

“…В ходе выполнения экспериментального исследования на животных с индуцированным стрептозотоцином СД оценивали эффективность применения арГПП-1 лираглутида по сравнению с контролем по влиянию на гиперплазию интимы коронарных артерий после имплантации стента за счет регуляции вариабельности уровня глюкозы в крови, а также за счет влияния на уровень инфламмасома NLRP3, который участвует в активации каспаз 1-го и 5-го типов, и соответственно, в образовании интерлейкина-1β и интерлейкина-18, т. е. цитокинов, регулирующих уровень воспаления в сосудистой стенке [34]. Кроме того, оценивали влияние применения лираглутида на концентрацию противовоспалительного цитокина интерлейкина-10 в крови.…”