ABSTRACT
Atherosclerosis, a chronic disorder and the main pathogenesis of various cardiovascular diseases, is initiated by theformation of the macrophage foam cell at the subendothelial layer of the blood vessel wall. This study aimed toinvestigate the anti-atherosclerosis activity of n-hexane extract of Eleutherine americana Merr. (E. americana) onhuman macrophage through in vitro induction with oxidized-Low Density Lipoprotein (ox-LDL). The macrophagewas obtained from peripheral blood mononuclear cells (PBMCs) that were isolated from the serum of a healthy male.After the monocytes were maturely differentiated, the n-hexane extract of E. americana with a dose of 0.25, 1, and2 mg/ml was added before stimulation with ox-LDL. The foam cell was determined through Oil Red O staining, theexpressions of Toll-Like Receptor 4 (TLR4) and Adenosine Triphosphate-binding cassette transporter A1/G1 (ABCA1/ABCG1) were measured by immunofluorescence, and the activity of peroxisome-proliferator-activator receptor γ(PPARγ) was measured through Enzyme-linked immunosorbent assay. The results demonstrated that the foam celland the expression of TLR4 on the group with E. americana extract treatment were lower than the ox-LDL group (p <0.05). The expression of ABCA1 and ABCG1 on the group that was given the extract was higher than ox-LDL group(p < 0.05). This study concluded that the n-hexane extract of E. americana demonstrated anti-atherosclerosis activityon human macrophage induced with ox-LDL.
ABSTRACT
The efflux of cholesterol from macrophage to liver is known as reverse cholesterol transport (RCT). Impairedcholesterol efflux leads to cholesterol accumulation in macrophages. Therefore, how to increasing cholesterol effluxmay be an effective strategy for atherosclerosis prevention. Key molecules that play a vital role in the efflux ofcholesterol from macrophage are Adenosin Tri Phosphate (ATP)-binding casette transporters A1 and G. This study wasundertaken to clarify the effect of Catechins on the expression of specific transporters such as ATP-binding cassettesub-family A member 1 (ABCA1), ATP-binding cassette sub-family G member 1 (ABCG1) from macrophage to liver,and scavenger receptor class B type I (SRB1). This research was done on Wistar rats induced atherogenic diets. SRB1is one of the transporters to facilitate the delivery of cholesterol from the macrophage to the liver. The SRB1 pathwaymediated the selective uptake of cholesteryl ester. Catechins significantly increased the mRNA expression of ABCA1and ABCG1 in aorta as well as SRB1 of liver also increased. Thus, Catechins decreased the total cholesterol levels inaorta and serum. Catechins can be developed as a potential agent to increase ABCA1 to inhibit atherogenesis process.In conclusion, this study indicates that the potential anti-atherogenic properties of Catechins could be explained, atleast in part, as being due to upregulated expression of ABCA1, ABCG1, and SRB1 through activation liver X receptorsignaling pathway
ABSTRACT
The efflux of cholesterol from macrophage to liver is known as reverse cholesterol transport (RCT). Impairedcholesterol efflux leads to cholesterol accumulation in macrophages. Therefore, how to increasing cholesterol effluxmay be an effective strategy for atherosclerosis prevention. Key molecules that play a vital role in the efflux ofcholesterol from macrophage are Adenosin Tri Phosphate (ATP)-binding casette transporters A1 and G. This study wasundertaken to clarify the effect of Catechins on the expression of specific transporters such as ATP-binding cassettesub-family A member 1 (ABCA1), ATP-binding cassette sub-family G member 1 (ABCG1) from macrophage to liver,and scavenger receptor class B type I (SRB1). This research was done on Wistar rats induced atherogenic diets. SRB1is one of the transporters to facilitate the delivery of cholesterol from the macrophage to the liver. The SRB1 pathwaymediated the selective uptake of cholesteryl ester. Catechins significantly increased the mRNA expression of ABCA1and ABCG1 in aorta as well as SRB1 of liver also increased. Thus, Catechins decreased the total cholesterol levels inaorta and serum. Catechins can be developed as a potential agent to increase ABCA1 to inhibit atherogenesis process.In conclusion, this study indicates that the potential anti-atherogenic properties of Catechins could be explained, atleast in part, as being due to upregulated expression of ABCA1, ABCG1, and SRB1 through activation liver X receptorsignaling pathway.
ABSTRACT
Liver X receptor (LXR) plays an important role in reverse cholesterol transport (RCT), and activation of LXR could reduce atherosclerosis. In the present study we used a cell-based screening method to identify new potential LXRβ agonists. A novel benzofuran-2-carboxylate derivative was identified with LXRβ agonist activity: E17110 showed a significant activation effect on LXRβ with an EC50 value of 0.72 μmol/L. E17110 also increased the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) in RAW264.7 macrophages. Moreover, E17110 significantly reduced cellular lipid accumulation and promoted cholesterol efflux in RAW264.7 macrophages. Interestingly, we found that the key amino acids in the LXRβ ligand-binding domain had distinct interactions with E17110 as compared to TO901317. These results suggest that E17110 was identified as a novel compound with LXRβ agonist activity in vitro via screening, and could be developed as a potential anti-atherosclerotic lead compound.
ABSTRACT
microRNAs (miRNAs or miRs) are small non-coding RNAs that are involved in post-transcriptional regulation of their target genes in a sequence-specific manner. Emerging evidence demonstrates that miRNAs are critical regulators of lipid synthesis, fatty acid oxidation and lipoprotein formation and secretion. Dysregulation of miRNAs disrupts gene regulatory network, leading to metabolic syndrome and its related diseases. In this review, we introduced epigenetic and transcriptional regulation of miRNAs expression. We emphasized on several representative miRNAs that are functionally involved into lipid metabolism, including miR-33/33(⁎), miR122, miR27a/b, miR378/378(⁎), miR-34a and miR-21. Understanding the function of miRNAs in lipid homeostasis may provide potential therapeutic strategies for fatty liver disease.
ABSTRACT
Objective To identify potential linkage of cholesterol efflux with the expressions of ATP-binding cas-sette receptor A1 (ABCA1), ABCG1 and scavenger receptor B1 (SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus. Methods and Results Blood was collected from subjects with or without type 2 diabetes mellitus. Peripheral blood monocytes were differentiated for 72 hours into macrophages, and cholesterol efflux assays, Real-time quantitative PCR and western blot were performed. Macrophages from patients with type 2 diabetes mellitus showed a reduction in cholesterol efllux. The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced. In contrast, the expression of ABCA1 and SR-B1 was not significantly different in both control subjects and diabetic patients. In addition, cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1. Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus. This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.
ABSTRACT
The ATP-binding cassette transporters ABCA1 and ABCG1 are highly expressed in macrophage-derived foam cells and promote reverse cholesterol efflux via biogenesis of high-density lipoproteins. The aim of this study was to analyze the direct effects of bioactive factors related to the metabolic syndrome on macrophage transcript levels of all 47 human ABC transporters. Using in vitro M-CSF predifferentiated macrophages and TaqMan low density arrays we could show that linoleic acid, palmitic acid, and high glucose levels have a major impact on ABCA1 and ABCG1 expression but do not strongly affect most other human ABC transporters. In Western blot experiments we demonstrate that ABCA1 and ABCG1 protein levels are synchronously suppressed by high glucose levels and the omega6-unsaturated fatty acid linoleic acid. We conclude that metabolites associated with the metabolic syndrome enhance the formation of atherosclerotic lesions by diminishing the reverse cholesterol transport function of ABCA1 and ABCG1.
Subject(s)
Humans , ATP-Binding Cassette Transporters/genetics , Cells, Cultured , Fatty Acids/genetics , Fatty Acids, Unsaturated/genetics , Gene Expression Profiling , Gene Expression Regulation , Glucose/genetics , Macrophages/metabolism , RNA, Messenger/metabolism , Time FactorsABSTRACT
Objective To identify potential linkage of cholesterol efflux with the expressions of ATP-binding cassette receptor A1(ABCA1),ABCG1 and scavenger receptor B1(SR-B1) in monocytes derived macrophages of patients with type 2 diabetes mellitus.Methods and Results Blood was collected from subjects with or without type 2 diabetes mellitus.Peripheral blood monocytes were differentiated for 72 hours into macrophages,and cholesterol efflux assays,Real-time quantitative PCR and western blot were performed.Macrophages from patients with type 2 diabetes mellitus showed a reduction in cholesterol efflux.The mRNA and protein expressions of ABCG1 in macrophages from patients with type 2 diabetes mellitus were significantly reduced.In contrast,the expression of ABCA1 and SR-B1 was not significantly different in both control subjects and diabetic patients.In addition,cellular cholesterol efflux from macrophages to autologous serum and pool serum was significantly correlated with the expression of ABCG1.Conclusion ABCG1 expression and cholesterol efflux are reduced in patients with type 2 diabetes mellitus.This impaired cholesterol efflux significantly correlates with decreased expression of ABCG1.