scholarly journals Maslinic acid suppresses macrophage foam cell formation via inhibition of LDL oxidation and cholesterol efflux

2018 ◽  
Vol 9 ◽  
Author(s):  
Su Wen Phang ◽  
Bee Kee OOI ◽  
Nafees Ahmed ◽  
Wei Hsum Yap
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Maslinic Acid

A reliable and reproducible assay for determining the effect of natural product on macrophages lipid uptake and cholesterol efflux: A case study of maslinic acid

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Bee Kee Ooi ◽  
Nafees Ahemad ◽  
Wei Hsum Yap
Keyword(s):  
Natural Product ◽  
Fluorescence Intensity ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Lipid Uptake ◽  
Macrophage Foam Cell ◽  
Maslinic Acid

Macrophage foam cell formation represents a key feature that contributes to the development of atherosclerotic lesions. Assessment of cardioprotective natural compounds targeting macrophage foam cell formation processes including lipid uptake and cholesterol efflux could lead to the identification of potential lead compounds for development into novel anti-atherosclerotic drugs. In this case study, maslinic acid, a natural product was used to study the effect on lipid uptake and cholesterol efflux in THP-1-derived macrophages.  Oil red O (ORO) staining and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-labeled oxidized low-density lipoprotein (Dil-labeled oxLDL) uptake assays were performed to determine lipid uptake by macrophages while cholesterol efflux was assessed using 3-hexanoyl-NBD labeled cholesterol. ORO-stained images were further analyzed using ImageJ analysis software to determine intracellular lipid droplets accumulation and flow cytometric analysis of mean fluorescence intensity were obtained to quantify Dil-labeled oxLDL uptake by macrophages. Meanwhile, 3-hexanoyl-NBD labeled cholesterol uptake and efflux from THP-1-derived macrophages were characterized. The fluorescence intensity values obtained from the medium and cell lysates were then converted into percentage of cholesterol efflux. The results have shown that incubation with maslinic acid suppressed oxLDL-induced macrophage foam cell formation which may be contributed from its effect in reducing lipid uptake and enhancing cholesterol efflux. In conclusion, the optimized ORO staining, Dil-labeled oxLDL uptake, and fluorescent-labeled cholesterol efflux assays provide reproducible and reliable results for assessment of foam cells formation.

scholarly journals Anti-Atherosclerotic Activity of (3R)-5-Hydroxymellein from an Endophytic Fungus Neofusicoccum parvum JS-0968 Derived from Vitex rotundifolia through the Inhibition of Lipoproteins Oxidation and Foam Cell Formation

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 715
Author(s):  
Jae-Yong Kim ◽  
Soonok Kim ◽  
Sang Hee Shim
Keyword(s):  
Conformational Changes ◽  
Endophytic Fungus ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Neofusicoccum Parvum

An endophytic fungus, Neofusicoccum parvum JS-0968, was isolated from a plant, Vitex rotundifolia. The chemical investigation of its cultures led to the isolation of a secondary metabolite, (3R)-5-hydroxymellein. It has been reported to have antifungal, antibacterial, and antioxidant activity, but there have been no previous reports on the effects of (3R)-5-hydroxymellein on atherosclerosis. The oxidation of lipoproteins and foam cell formation have been known to be significant in the development of atherosclerosis. Therefore, we investigated the inhibitory effects of (3R)-5-hydroxymellein on atherosclerosis through low-density lipoprotein (LDL) and high-density lipoprotein (HDL) oxidation and macrophage foam cell formation. LDL and HDL oxidation were determined by measuring the production of conjugated dienes and malondialdehyde, the amount of hyperchromicity and carbonyl content, conformational changes, and anti-LDL oxidation. In addition, the inhibition of foam cell formation was measured by Oil red O staining. As a result, (3R)-5-hydroxymellein suppressed the oxidation of LDL and HDL through the inhibition of lipid peroxidation, the decrease of negative charges, the reduction of hyperchromicity and carbonyl contents, and the prevention of apolipoprotein A-I (ApoA-I) aggregation and apoB-100 fragmentation. Furthermore, (3R)-5-hydroxymellein significantly reduced foam cell formation induced by oxidized LDL (oxLDL). Taken together, our data show that (3R)-5-hydroxymellein could be a potential preventive agent for atherosclerosis via obvious anti-LDL and HDL oxidation and the inhibition of foam cell formation.

Leptin modulates ACAT1 expression and cholesterol efflux from human macrophages

2009 ◽  
Vol 297 (2) ◽  
pp. E474-E482 ◽  
Author(s):  
Shigeki Hongo ◽  
Takuya Watanabe ◽  
Shigeko Arita ◽  
Tomoko Kanome ◽  
Haruaki Kageyama ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Efflux ◽  
Leptin Receptor ◽  
Foam Cell ◽  
Cell Formation ◽  
Human Monocyte ◽  
Foam Cell Formation ◽  
Monocytic Differentiation ◽  
Macrophage Foam Cell ◽  
Cholesteryl Ester Accumulation

Leptin is an adipose tissue-derived hormone implicated in atherosclerosis and macrophage foam cell formation. The current study was conducted to examine the effect of leptin on cholesteryl ester accumulation in human monocytes/macrophages. Exogenously added leptin at 5 nM during differentiation of monocytes into macrophages for 7 days accelerated acetylated LDL (acetyl-LDL)-induced cholesteryl ester accumulation by 30–50%. Leptin did not affect endocytic uptake of acetyl-LDL; however, it increased ACAT activity 1.8-fold and ACAT-1 protein expression 1.9-fold. Among the four ACAT-1 mRNA transcripts, two shorter transcripts (2.8 and 3.6 kb) were upregulated ∼1.7-fold upon leptin treatment. The enhanced expression of ACAT-1 protein by leptin was suppressed by inhibitors of Janus-activated kinase2 (JAK2) and phosphatidylinositol 3-kinase (PI3K). HDL-mediated cholesterol efflux was suppressed by leptin, which was canceled by K-604, an ACAT-1 inhibitor. Expression of long form of leptin receptor was upregulated during monocytic differentiation into macrophages and sustained after differentiation. Thus, the results suggest that leptin accelerates cholesteryl ester accumulation in human monocyte-derived macrophages by increasing ACAT-1 expression via JAK2 and PI3K, thereby suppressing cholesterol efflux.

scholarly journals SIRT 6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox‐ LDL condition

FEBS Journal ◽  
2017 ◽  
Vol 284 (9) ◽  
pp. 1324-1337 ◽  
Author(s):  
Jiangping He ◽  
Guangya Zhang ◽  
Qi Pang ◽  
Cong Yu ◽  
Jie Xiong ◽  
...  
Keyword(s):  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell

scholarly journals Hesperetin inhibits foam cell formation and promotes cholesterol efflux in THP-1-derived macrophages by activating LXRα signal in an AMPK-dependent manner

2021 ◽  
Author(s):  
Xuanjing Chen ◽  
Dezhi Zou ◽  
Xiaoling Chen ◽  
Huanlin Wu ◽  
Danping Xu
Keyword(s):  
Cholesterol Efflux ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Foam Cell ◽  
Cell Formation ◽  
Underlying Mechanism ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Protective Effects ◽  
Macrophage Foam Cell

AbstractCholesterol efflux from macrophages is the first step of reverse cholesterol transport (RCT), whose increase inhibits cholesterol accumulation and foam cell formation to suppress atherogenesis. Hesperetin has been reported to exert several protective effects on cardiovascular diseases, while little is known about the role of hesperetin and its underlying mechanism in macrophage foam cell formation. In this study, we sought to investigate the potential effects of hesperetin on foam cell formation and cholesterol efflux by using human macrophages, focusing on liver X receptor alpha (LXRα) and AMPK. We found that hesperetin treatment reduced foam cell formation, intracellular cholesterol levels and the cholesterol esterification rate, and increased cholesterol efflux in THP-1 macrophages. Hesperetin increased the levels of LXRα protein and its targets, including ABCA1, ABCG1, SR-BI, and phosphorylated-AMPK. Meanwhile, the hesperetin-induced increase in LXRα expression was further increased by the AMPK agonist and inhibited by an AMPK inhibitor. Meanwhile, hesperetin increased the levels of LXRα mRNA and its target genes, all of which were decreased in cells transfected with the AMPKα1/α2 small interfering RNA (siRNA). Furthermore, the hesperetin-induced inhibition of foam cell formation and promotion of cholesterol efflux were decreased by transfection of AMPKα1/α2 siRNA. In conclusions, We are the first to report that hesperetin activate AMPK in THP-1-derived macrophages. This activation upregulats LXRα and its targets, including ABCA1, ABCG1 and SR-BI, which significantly inhibits foam cell formation and promotes cholesterol efflux. Our results highlight the therapeutic potential of hesperetin to possibly reduce foam cell formation. This new mechanism might contribute the anti-atherogenic effects of hesperetin.

scholarly journals Glucose-Dependent Insulinotropic Polypeptide Suppresses Foam Cell Formation of Macrophages through Inhibition of the Cyclin-Dependent Kinase 5-CD36 Pathway

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 832
Author(s):  
Michishige Terasaki ◽  
Hironori Yashima ◽  
Yusaku Mori ◽  
Tomomi Saito ◽  
Yoshie Shiraga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
U937 Cells ◽  
Cyclin Dependent Kinase ◽  
Macrophage Foam Cell ◽  
Cyclin Dependent Kinase 5 ◽  
Gip Receptor ◽  
Cd36 Gene

Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and CD36 expression in, macrophages extracted from GIP receptor-deficient (Gipr−/−) and Gipr+/+ mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala2]GIP(1–42). Foam cell formation evaluated by esterification of free cholesterol to cholesteryl ester and CD36 gene expression in macrophages isolated from Gipr+/+ mice infused subcutaneously with [D-Ala2]GIP(1–42) were significantly suppressed compared with vehicle-treated mice, while these beneficial effects were not observed in macrophages isolated from Gipr−/− mice infused with [D-Ala2]GIP(1–42). When macrophages were isolated from Gipr+/+ and Gipr−/− mice, and then exposed to [D-Ala2]GIP(1–42), similar results were obtained. [D-Ala2]GIP(1–42) attenuated ox-LDL uptake of, and CD36 gene expression in, human U937 macrophages as well. Gene expression level of cyclin-dependent kinase 5 (Cdk5) was also suppressed by [D-Ala2]GIP(1–42) in U937 cells, which was corelated with that of CD36. A selective inhibitor of Cdk5, (R)-DRF053 mimicked the effects of [D-Ala2]GIP(1–42) in U937 cells. The present study suggests that GIP could inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor.

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