Ezetimibe suppresses cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling

Qin, Li; Yang, Yanjun; Yang, Yixin; Zhu, Neng; Gong, Yanling; Zhang, Caiping; Li, Shunxiang; Liao, Duan‐Fang

doi:10.1038/aps.2014.10

Cited by 7 publications

(8 citation statements)

References 48 publications

(45 reference statements)

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“…All cultures were incubated with serum-free media for 24 h prior to treatment. Cultures of VSMCs were divided into the following groups: control (5 mM glucose); HG (25 mM glucose); LIRA (100 nM; previously described dose [ 51 ]); HG + LIRA (25 mM glucose and 100 nM LIRA); osmotic (MG; 25 mM mannitol); HG + LY294002 (25 mM glucose and 50 μM LY294002 [ 52 ]); HG + LIRA + LY294002 (25 mM glucose, 100 nM LIRA, and 50 μM LY294002); HG + PD98059 (25 mM glucose and 50 μM PD98059 [ 53 ]); HG + LIRA + PD98059 (25 mM glucose, 100 nM LIRA, and 50 μM PD98059); and HG + LIRA + Exe(9–39) (25 mM glucose, 100 nM LIRA, and 200 nM Exe(9–39) [ 54 , 55 ]). All VSMCs cultures were pretreated with the indicated drugs 1 h prior to HG treatment with exception of Exe(9–39) treatment, which was added 30 min prior to HG treatment.…”

Section: Methodsmentioning

confidence: 99%

Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways

Shi

Jiang

et al. 2015

Cardiovasc Diabetol

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BackgroundAs a new anti-diabetic medicine, Liraglutide (LIRA), one of GLP-1 analogues, has been found to have an anti-atherosclerotic effect. Since vascular smooth muscle cells (VSMCs) play pivotal roles in the occurrence of diabetic atherosclerosis, it is important to investigate the role of LIRA in reducing the harmful effects of high-glucose (HG) treatment in cultured VSMCs, and identifying associated molecular mechanisms.MethodsPrimary rat VSMCs were exposed to low or high glucose-containing medium with or without LIRA. They were challenged with HG in the presence of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2, or glucagon-like peptide receptor (GLP-1R) inhibitors. Cell proliferation and viability was evaluated using a Cell Counting Kit-8. Cell migration was determined by Transwell migration and scratch wound assays. Flow cytometry and Western blotting were used to determine apoptosis and protein expression, respectively.ResultsUnder the HG treatment, VSMCs exhibited increased migration, proliferation, and phosphorylation of protein kinase B (Akt) and ERK1/2, along with reduced apoptosis (all p < 0.01 vs. control). These effects were significantly attenuated with LIRA co-treatment (all p < 0.05 vs. HG alone). Inhibition of PI3K kinase and ERK1/2 similarly attenuated the HG-induced effects (all p < 0.01 vs. HG alone). GLP-1R inhibitors effectively reversed the beneficial effects of LIRA on HG treatment (all p < 0.05).ConclusionsHG treatment may induce abnormal phenotypes in VSMCs via PI3K and ERK1/2 signaling pathways activated by GLP-1R, and LIRA may protect cells from HG damage by acting on these same pathways.

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Section: Methodsmentioning

confidence: 99%

Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways

Shi

Jiang

et al. 2015

Cardiovasc Diabetol

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“…Immune cues, such as activation of TLR4, can induce formation of foam cells from VSMC via activation of NF- κ B and induction of Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) [ 107 ]. Furthermore, molecules such as ezetimibe and TRPV1 have been shown to impede formation of VSMC-derived foam cells by preventing cholesterol accumulation [ 108 ] and promoting autophagy [ 109 ], respectively, highlighting the importance of these processes in this context. Recent research has also shown these cells carry cholesterol loads larger than previously considered, possibly linked to their relatively lower capacity for cholesterol release via ABCA1 and their ability to transdifferentiate towards a macrophage-like phenotype in advanced atherosclerosis [ 110 , 111 ].…”

Section: From Endothelial Dysfunction To Atherosclerosis: a Quick mentioning

confidence: 99%

Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

et al. 2015

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Cardiovascular disease (CVD) is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD.

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“…Caveolin-1 (Cav-1), a membrane scaffolding protein, is the main structural component of caveolae and plays a crucial role in autophagy-mediated maintenance of cellular cholesterol homeostasis and lipid transportation [ 18 ]. In adult rats fed with high-fat diets, RSV has been shown to down-regulate the expression of Cav-1 and induce autophagy in adipocytes, which are associated with the maintenance of the homeostasis in lipid metabolism [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in zebrafish (Danio rerio)

Ran

Lin

et al. 2017

PLoS ONE

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Defective lipid metabolism is associated with increased risk of various chronic diseases, such as obesity, cardiovascular diseases, and diabetes. Resveratrol (RSV), a natural polyphenol, has been shown the potential of ameliorating disregulations of lipid metabolism. The objective of this study was to investigate the effects of feed intake and RSV on lipid metabolism in zebrafish (Danio rerio). The adult males were randomly allocated to 6 groups: control (Con, 8 mg cysts/fish/day), control with 20 μmol/L RSV (Con+RSV), calorie restriction (CR, 5 mg cysts/fish/day), calorie restriction with RSV (CR+RSV), overfeed (OF, 60 mg cysts/fish/day), and overfeed with RSV (OF+RSV) groups. The treatment period was 8 weeks. Results showed that CR reduced body length, body weight, and condition factor of zebrafish. CR reduced levels of plasma triglyceride (TG) and induced protein expression of phosphorylated AMP-activated protein kinase-α (pAMPKα), silent information regulator 2 homolog 1 (Sirt1), and peroxisome proliferator activated receptor gamma coactivator-1α (PGC1α). RSV attenuated CR-induced pAMPKα/AMPKαincreases. RSV increased levels of Sirt1 protein in the OF zebrafish, and decreased OF-induced increase in peroxisome proliferator-activated receptor-γ (PPARγ) protein level. Additionally, RSV down-regulated caveolin-1 and up-regulated microtubule-associated protein 1 light chain 3 -II (LC3-II) protein levels in OF zebrafish. In conclusion, these results suggest that 1) CR reduces plasma TG level through activation of the AMPKα-Sirt1- PGC1α pathway; 2) under different dietary stress conditions RSV might regulate AMPK phosphorylation bi-directionally; 3) RSV might regulate lipid metabolism through the AMPKα-Sirt1-PPARγ pathway in OF zebrafish.

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Ezetimibe suppresses cholesterol accumulation in lipid-loaded vascular smooth muscle cells in vitro via MAPK signaling

Cited by 7 publications

References 48 publications

Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways

Liraglutide attenuates high glucose-induced abnormal cell migration, proliferation, and apoptosis of vascular smooth muscle cells by activating the GLP-1 receptor, and inhibiting ERK1/2 and PI3K/Akt signaling pathways

Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

Resveratrol ameliorates diet-induced dysregulation of lipid metabolism in zebrafish (Danio rerio)

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