Ezetimibe prevents myocardial remodeling in an obese rat model by inhibiting inflammation

Li, Xiaoxing; Zhao, Lang; Chang, Ying; Liu, Baoshan; Xu, Feng; Zhang, Cheng; Ji, Xiaoping; Chen, Yuguo; Li, Chuanbao

doi:10.18388/abp.2018_2597

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…The obesity model was established successfully by feeding HFD for 12 weeks, as evidenced by ndings consistent with previous reports [32][33][34]. LBP softly reversed the biochemical parameters, including TC, TG, ALT, AST, CREA, UA, HDL, LDL.…”

Section: Lbp Improved Biochemical Index In Obese Ratssupporting

confidence: 85%

Lycium Barbarum Polysaccharides Regulate the Gut Microbiota To Modulate Metabolites in High Fat Diet-Induced Obese Rats

Fan

Lü

et al. 2021

Preprint

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Previous studies had indicated that the gut microbiota was a main internal factor leading to obesity through energy storage and metabolic disorders. Lycium Barbarum Polysaccharides (LBP) have been discovered with a more protective effect on intestinal flora. But it is unclear whether LBP could regulate the gut microbiota to modulate metabolites, finally relieving obesity. A related study of high-throughput 16S rRNA sequencing and serum metabolomics profiling in LBP intervention on high fat diet-induced obese rats then explored the beneficial effects of LBP and the underlying mechanism. LBP affected lipid parameters such as total cholesterol, Triglyceride, and High-density lipoprotein. The gut microbiota result detected 16 types of the phylum of bacteria in total, while four of them (Bacteroidetes, Firmicutes, Proteobacteria, Deferribacteres) were significantly different. LBP upregulated the level of Firmicutes of obese rats. LBP might associate with the gut microbiota that participates in the membrane transport and metabolism of amino acid, carbohydrate, energy, and lipid. The serum metabolomics profiling of high-fat diet-induced obesity rats found over 30 differential metabolites between model and intervention groups. Primary metabolites include cortisol, glycohyocholic acid, homo-L-arginine, ursodeoxycholic acid, isoursodeoxycholic acid, glycoursocholic acid, 4-ethylphenylsulfate, deoxycholic acid, 7-hydroxy-3-oxocholanoic acid isomers, gly-phe, pipecolic acid, proline betaine, and pyrocatechol sulfate. Pathway analysis in serum found four disorder pathways: glycerophospholipid metabolism, glycine-serine-threonine metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism. The studies revealed that LBP treatment increased the diversity of fecal microorganisms and reduced metabolic disorders in obese rats. LBP ameliorated metabolic disorders and rebalanced the gut microbiome.

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Section: Lbp Improved Biochemical Index In Obese Ratssupporting

confidence: 85%

Lycium Barbarum Polysaccharides Regulate the Gut Microbiota To Modulate Metabolites in High Fat Diet-Induced Obese Rats

Fan

Lü

et al. 2021

Preprint

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“…Li et al . (2018) [ 31 ] report that obese rats treated with ezetimibe (10 mg/kg/day; eight weeks) present lower ICAM-1 levels in myocardial tissue than untreated obese rats.…”

Section: Discussionmentioning

confidence: 99%

A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol

et al. 2021

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Dyslipidemia, atherosclerosis, and cardiovascular events can be prevented, or treated, using statins, alone or in combination with ezetimibe. The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe and their combinations on endothelial cells damaged by oxidized cholesterol. HUVEC cultures were stimulated for 20 hours with atorvastatin (5 μM; 2793 ng/mL), rosuvastatin (10 μM; 4815 ng/mL), ezetimibe (1.22 μM; 500 ng/mL), atorvastatin plus ezetimibe (5 μM + 1.22 μM; 2793 ng/mL + 500 ng/mL) and rosuvastatin plus ezetimibe (10 μM + 1.22 μM; 4815 ng/mL + 500ng/mL) in separate groups, with or without 25-hydroxycholesterol pre-incubation (24.83 μM; 10 μg/mL; four hours then washout). HUVEC integrity was measured in the RTCA-DP xCELLigence system. The mRNA expression and protein levels of ZO-1, OCLN, ICAM-1 were analyzed by real-time PCR and ELISA. Pre-incubation with 25-OHC resulted in decreased endothelial cell integrity (p<0.001), decreased expression of ZO-1 mRNA (p<0.05) and protein levels (p<0.05), OCLN mRNA (p<0.05) and protein levels (p<0.05) and increased ICAM-1 mRNA (p<0.001) and protein levels (p<0.001) compared to the control group. Incubation with rosuvastatin (12h p<0.01; 24h p<0.001) and atorvastatin (only 12h p<0.05) restored HUVEC integrity. Subsequent incubation with rosuvastatin increased ZO-1 mRNA (p<0.001) and protein (p<0.001) levels. Subsequent addition of ezetimibe increased ZO-1 mRNA level (p<0.001) but not protein level. Furthermore, only incubation with rosuvastatin increased OCLN mRNA (p<0.05) and protein (p<0.05) levels. In each drug-stimulated group, both ICAM-1 mRNA and protein levels were reduced after initial incubation with oxysterol (p<0.05). 25-hydroxycholesterol disrupts endothelial integrity, decreases the mRNA and protein levels of tight junction, and increases those of intercellular adhesion molecules. Both rosuvastatin and atorvastatin can improve endothelial integrity, but only rosuvastatin can completely abolish the effect of oxysterol. The combination of statins with ezetimibe has less direct effect on the endothelial barrier than the statins alone.

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“…It has been reported that ezetimibe confers additional beneficial effects other than lowering blood lipid levels. In animal models, ezetimibe reduced inflammatory response [50][51][52] and promoted autophagy, which resulted in neuroprotection or improvement of nonalcoholic fatty liver disease (NAFLD) [24,53] via AMP protein kinase (AMPK) activation and inhibition of NLR family pyrin domain containing 3 (NLRP3) inflammasome [23]. In addition, ezetimibe is known to activate nuclear factor erythroid 2-related factor 2 (Nrf2) and to reduce oxidative stress in animal models [54].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Renal Effects of Ezetimibe–Statin Combination versus Statin Monotherapy: A Propensity-Score-Matched Analysis

Bae

Hong

Lee

et al. 2020

JCM

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Neither lowering of blood lipid levels nor treatment with statins definitively improves renal outcomes. Ezetimibe, a non-statin antilipidemic agent, is known to not only decrease blood lipid levels but also reduce inflammatory response and activate autophagy. We evaluated the effect of adding ezetimibe to a statin on renal outcome compared with statin monotherapy by analyzing longitudinal data of 4537 patients treated with simvastatin 20 mg plus ezetimibe 10 mg (S + E) or simvastatin 20 mg alone (S) for more than 180 days. A propensity-score-based process was used to match baseline characteristics, medical history, and estimated glomerular filtration rate (eGFR) between S + E and S groups. Changes in serum creatinine and incidence of renal events, defined as doubling of serum creatinine to ≥1.5 mg/dL or occurrence of end-stage renal disease after the first day of treatment initiation, were compared between the groups. Among 3104 well-matched patients with a median follow-up of 4.2 years, the S + E group showed a significantly lower risk of renal events than the S group (hazard ratio 0.58; 95% CI 0.35-0.95, P = 0.032). In addition, the S + E group tended to preserve renal function compared with the S group throughout follow-up, as assessed by serum creatinine changes (P-values for time-group interactions <0.001). These data support the beneficial effects on renal function when combining ezetimibe with a statin.

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Ezetimibe prevents myocardial remodeling in an obese rat model by inhibiting inflammation

Cited by 9 publications

References 30 publications

Lycium Barbarum Polysaccharides Regulate the Gut Microbiota To Modulate Metabolites in High Fat Diet-Induced Obese Rats

Lycium Barbarum Polysaccharides Regulate the Gut Microbiota To Modulate Metabolites in High Fat Diet-Induced Obese Rats

A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol

Comparison of Renal Effects of Ezetimibe–Statin Combination versus Statin Monotherapy: A Propensity-Score-Matched Analysis

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