Grape seed proanthocyanidins suppressed macrophage foam cell formation by miRNA-9 <i>via</i> targeting ACAT1 in THP-1 cells

Shao, Dongyan; Di, Yichao; Lian, Ziyang; Zhu, Bing; Xu, Xiaoguang; Guo, Dan; Huang, Qingsheng; Jiang, Chunmei; Kong, Jie; Shi, Junling

doi:10.1039/c9fo02352f

Cited by 27 publications

(18 citation statements)

References 42 publications

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“…ABCA1 and ABCG1 belong to the ATP-binding cassette transporter (ABC) protein family. Their function is to coordinate the export of cholesterol from the cells [ 60 , 61 ]. Cholesterol is transported from outside the cell to the inside of the cell through LDLR [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles

et al. 2021

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This study evaluated the differences in metabolites between cumulus cells (CCs) and mural granulosa cells (MGCs) from human preovulatory follicles to understand the mechanism of oocyte maturation involving CCs and MGCs. CCs and MGCs were collected from women who were undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment. The differences in morphology were determined by immunofluorescence. The metabolomics of CCs and MGCs was measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) followed by quantitative polymerase chain reaction (qPCR) and western blot analysis to further confirm the genes and proteins involved in oocyte maturation. CCs and MGCs were cultured for 48 h in vitro, and the medium was collected for detection of hormone levels. There were minor morphological differences between CCs and MGCs. LC-MS/MS analysis showed that there were differences in 101 metabolites between CCs and MGCs: 7 metabolites were upregulated in CCs, and 94 metabolites were upregulated in MGCs. The metabolites related to cholesterol transport and estradiol production were enriched in CCs, while metabolites related to antiapoptosis were enriched in MGCs. The expression of genes and proteins involved in cholesterol transport (ABCA1, LDLR, and SCARB1) and estradiol production (SULT2B1 and CYP19A1) was significantly higher in CCs, and the expression of genes and proteins involved in antiapoptosis (CRLS1, LPCAT3, and PLA2G4A) was significantly higher in MGCs. The level of estrogen in CCs was significantly higher than that in MGCs, while the progesterone level showed no significant differences. There are differences between the metabolomes of CCs and MGCs. These differences may be involved in the regulation of oocyte maturation.

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Section: Discussionmentioning

confidence: 99%

The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles

et al. 2021

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“…Mechanically, PB2 inhibits foam cell formation and pyrin domain containing 3 inflammasome activation, and it activates PPARγ to induce M2 phenotype of mouse macrophages. All these beneficial effects may be attributed to the reduction of PB2 on the risk of atherosclerosis [16,[40][41][42][43]. However, the anti-atherosclerotic effects of PB2 on apoE −/− mice and the underlying mechanisms remain unknown.…”

Section: Discussionmentioning

confidence: 99%

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

et al. 2021

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Vascular calcification is strongly associated with atherosclerotic plaque burden and plaque instability. The activation of extracellular signal-regulated kinase 1/2 (ERK1/2) increases runt related transcription factor 2 (RUNX2) expression to promote vascular calcification. Procyanidin B2 (PB2), a potent antioxidant, can inhibit ERK1/2 activation in human aortic smooth muscle cells (HASMCs). However, the effects and involved mechanisms of PB2 on atherosclerotic calcification remain unknown. In current study, we fed apoE-deficient (apoE−/−) mice a high-fat diet (HFD) while treating the animals with PB2 for 18 weeks. At the end of the study, we collected blood and aorta samples to determine atherosclerosis and vascular calcification. We found PB2 treatment decreased lesions in en face aorta, thoracic, and abdominal aortas by 21.4, 24.6, and 33.5%, respectively, and reduced sinus lesions in the aortic root by 17.1%. PB2 also increased α-smooth muscle actin expression and collagen content in lesion areas. In the aortic root, PB2 reduced atherosclerotic calcification areas by 75.8%. In vitro, PB2 inhibited inorganic phosphate-induced osteogenesis in HASMCs and aortic rings. Mechanistically, the expression of bone morphogenetic protein 2 and RUNX2 were markedly downregulated by PB2 treatment. Additionally, PB2 inhibited ERK1/2 phosphorylation in the aortic root plaques of apoE−/− mice and calcified HASMCs. Reciprocally, the activation of ERK1/2 phosphorylation by C2-MEK1-mut or epidermal growth factor can partially restore the PB2-inhibited RUNX2 expression or HASMC calcification. In conclusion, our study demonstrates that PB2 inhibits vascular calcification through the inactivation of the ERK1/2-RUNX2 pathway. Our study also suggests that PB2 can be a potential option for vascular calcification treatment.

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“…( Tall and Yvan-Charvet, 2015 ). This happens due to the altered regulation of lipid metabolism caused by the disturbance of intracellular cholesterol influx and efflux and the intracellular cholesterol metabolism ( Shao et al, 2020 ). Therefore, regulatory proteins such as ACAT1, SR-A and ABCA1, which mediate processes in the cholesterol metabolism pathway, are critical in regulating macrophage cholesterol accumulation.…”

Section: Discussionmentioning

confidence: 99%

Multi-Omics Integration to Reveal the Mechanism of Hepatotoxicity Induced by Dictamnine

Tian

et al. 2021

Front. Cell Dev. Biol.

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Herb-induced liver injury (HILI) has become a great concern worldwide due to the widespread usage of herbal products. Among these products is Dictamni Cortex (DC), a well-known Traditional Chinese Medicine (TCM), widely used to treat chronic dermatosis. Dictamni Cortex has drawn increasing attention because of its hepatotoxicity caused by the hepatotoxic component, dictamnine. However, the potential hepatotoxicity mechanism of dictamnine remains unclear. Therefore, this study aimed to use the multi-omics approach (transcriptomic, metabolomic, and proteomic analyses) to identify genes, metabolites, and proteins expressions associated with dictamnine-induced hepatotoxicity. A study on mice revealed that a high dose of dictamnine significantly increases serum aspartate aminotransferase (AST) activity, total bilirubin (TBIL), and direct bilirubin (DBIL) levels, the relative liver weight and liver/brain weight ratio in female mice (P < 0.05 and P < 0.01), compared to the normal control group. Liver histologic analysis further revealed a high dose of dictamnine on female mice caused hepatocyte vesicular steatosis characterized by hepatocyte microvesicles around the liver lobules. The expressed genes, proteins, and metabolites exhibited strong associations with lipid metabolism disorder and oxidative stress. Dictamnine caused increased oxidative stress and early hepatic apoptosis via up-regulation of glutathione S transferase a1 (GSTA1) and Bax/Bcl-2 ratio and down-regulation of the antioxidative enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase 1 (GPx-1). Besides, the up-regulation of Acyl-CoA synthetase long-chain family member 4 (ACSL4) and down-regulation of acetyl-coa acetyltransferase 1 (ACAT1) and fatty acid binding protein 1 (FABP-1) proteins were linked to lipid metabolism disorder. In summary, dictamnine induces dose-dependent hepatotoxicity in mice, which impairs lipid metabolism and aggravates oxidative stress.

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Grape seed proanthocyanidins suppressed macrophage foam cell formation by miRNA-9 via targeting ACAT1 in THP-1 cells

Abstract: Grape seed proanthocyanidins inhibited cholesterol esterification by miRNA-9 via targeting ACAT1 to suppress the macrophage foam cell formation.

Cited by 27 publications

References 42 publications

The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles

The Differential Metabolomes in Cumulus and Mural Granulosa Cells from Human Preovulatory Follicles

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway

Multi-Omics Integration to Reveal the Mechanism of Hepatotoxicity Induced by Dictamnine

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