Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis

Volobueva, Alexandrina S.; Zhang, Dongwei; Grechko, Andrey V.; Orekhov, Alexander N.

doi:10.1016/j.crvasa.2018.06.006

Cited by 17 publications

(17 citation statements)

References 53 publications

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“…Previous studies have mentioned the association of cholesterol efflux capacity in relation to atherosclerosis [37]. Accumulation of cholesterol in foam cell macrophages will result in plaque formation that leads to atherosclerosis [38][39][40]. Our data obtained from cholesterol efflux assay has demonstrated the capacity of punicalagin to enhance cholesterol efflux in IFN-γ-induced THP-1 macrophages.…”

Section: Discussionsupporting

confidence: 53%

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Almowallad

Huwait²,

Almassabi

et al. 2020

Pharmaceuticals

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Atherosclerosis may lead to cardiovascular diseases (CVD), which are the primary cause of death globally. In addition to conventional therapeutics for CVD, use of nutraceuticals that prevents cholesterol deposition, reduce existing plaques and hence anti-atherosclerotic effects of nutraceuticals appeared to be promising. As such, in the present study we evaluated the beneficial effects of punicalagin, a phytochemical against an atherosclerotic cell model in vitro. Cytotoxicity assays were examined for 10 µM concentration of punicalagin on THP-1 macrophages. Real-time-polymerase chain reaction (RT-PCR) was used to analyze monocyte chemoattractant protein-1 (MCP-1) and Intercellular adhesion molecule (ICAM-1) expressions. Monocyte migration and cholesterol efflux assays were performed to investigate punicalagin's further impact on the key steps of atherosclerosis. Cytotoxicity assays demonstrated no significant toxicity for punicalagin (10 µM) on THP-1 macrophages. Punicalagin inhibited the IFN-γ-induced overexpression of MCP-1 and ICAM-1 in macrophages by 10 fold and 3.49 fold, respectively, compared to the control. Punicalagin also reduced the MCP-1- mediated migration of monocytes by 28% compared to the control. Percentages of cellular cholesterol efflux were enhanced in presence or absence of IFN-γ by 88% and 84% compared to control with 58 %and 62%, respectively. Punicalagin possesses anti-inflammatory and anti-atherosclerotic effects. Punicalagin also did not exhibit any cytotoxicity and therefore can be considered a safe and potential candidate for the treatment and prevention of atherosclerosis.

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Section: Discussionsupporting

confidence: 53%

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Almowallad

Huwait²,

Almassabi

et al. 2020

Pharmaceuticals

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“…Inflammation also represents a pivotal step in atherosclerosis initiation and progression, in that it favors the sustained recruitment of circulating monocytes within vascular lesions and supports their maturation in macrophages and eventually foam cells. 4 The considerable intracellular accumulation of oxLDL in macrophages reduces the ability of the cells to metabolize cholesterol 46 and generate reactive oxygen species triggering and sustaining local inflammation. Thus, controlling both oxLDL transport in and out of cells and the local state of inflammation may have dramatic implications in halting and possibly reversing atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Francesco

Gurgone

Palomba

et al. 2020

ACS Appl. Mater. Interfaces

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Macrophage inflammation and maturation into foam cells, following the engulfment of oxidized low-density lipoproteins (oxLDL), are major hallmarks in the onset and progression of atherosclerosis. Yet, chronic treatments with anti-inflammatory agents, such as methotrexate (MTX), failed to modulate disease progression, possibly for the limited drug bioavailability and plaque deposition. Here, MTX–lipid conjugates, based on 1,2-distearoyl- sn -glycero-3-phosphoethanolamine (DSPE), were integrated in the structure of spherical polymeric nanoparticles (MTX-SPNs) or intercalated in the lipid bilayer of liposomes (MTX-LIP). Although, both nanoparticles were colloidally stable with an average diameter of ∼200 nm, MTX-LIP exhibited a higher encapsulation efficiency (>70%) and slower release rate (∼50% at 10 h) compared to MTX-SPN. In primary bone marrow derived macrophages (BMDMs), MTX-LIP modulated the transcellular transport of oxLDL more efficiently than free MTX mostly by inducing a 2-fold overexpression of ABCA1 (regulating oxLDL efflux), while the effect on CD36 and SRA-1 (regulating oxLDL influx) was minimal. Furthermore, in BMDMs, MTX-LIP showed a stronger anti-inflammatory activity than free MTX, reducing the expression of IL-1β by 3-fold, IL-6 by 2-fold, and also moderately of TNF-α. In 28 days high-fat-diet-fed apoE –/– mice, MTX-LIP reduced the mean plaque area by 2-fold and the hematic amounts of RANTES by half as compared to free MTX. These results would suggest that the nanoenhanced delivery to vascular plaques of the anti-inflammatory DSPE-MTX conjugate could effectively modulate the disease progression by halting monocytes’ maturation and recruitment already at the onset of atherosclerosis.

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“…The decaffeinated coffee and green tea extract reduced CD36 and increased ABCA1 expression in ox-LDL stimulated macrophages Foam cells could be formed due to a dysregulation of the lipid metabolism, which was determined by the continuous uptake of ox-LDL and failure in lipid efflux from macrophages. 1,2,6 The endocytosis of ox-LDL is mainly regulated by CD36, 8,9 whereas ABCA1 plays a significant role in cholesterol efflux. 32,33 Thus, this study aimed to investigate the effect of the extract in the cells examined using the immunofluorescence technique.…”

Section: Resultsmentioning

confidence: 99%

“…1,2 However, atherosclerosis is the etiologic agent of various cardiovascular diseases that cause high morbidity and mortality worldwide, especially during the ongoing COVID-19 pandemic. [3][4][5] The crosstalk interaction between inflammation and lipid metabolism disturbances in macrophages are two key factors that determine foam cell formation 6,7 Upregulation of CD36 expression causes oxLDL endocytosis. 8,9 Thus, lipid accumulation inside macrophages leads to endoplasmic reticulum (ER) stress, and stimulates the production of inflammatory cytokines through the activation of nuclear factor kappa B (NFκB) signalling and the reduction of anti-inflammatory cytokines.…”

Section: Introductionmentioning

confidence: 99%

Decaffeinated coffee and green tea extract inhibit foam cell atherosclerosis by lowering inflammation and improving cholesterol influx/efflux balance through upregulation of PPARγ and miR-155

et al. 2021

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Background: Foam cells are markers of atherosclerosis and characterise advanced atherosclerotic plaque, stimulated by inflammation caused by high lipid levels in macrophages. The combination of decaffeinated coffee and green tea extract (DCGTE) has been suggested to have a role in foam cell inhibition. Objective: we investigated the inhibiting role of DCGTE against foam cell formation, through modulation of the inflammation process and cholesterol metabolism in macrophage colony stimulating factor- (M-CSF) and oxidized low-density lipoprotein (oxLDL)-exposed macrophages. Methods: Coffee and green tea were extracted by filtration and infusion respectively, and underwent decaffeination using active carbon and blanching methods, respectively. Cells were administered 160/160 and 320/320μg/ml of DCGTE. Foam cell formation was observed using a light microscope after staining with Oil Red O (ORO), and the accumulation of lipids in macrophages with ELISA. Observations of lipid influx and efflux were determined through semiquantitative cluster differentiation 36 (CD36) and ATP binding cassette transporter A1 (ABCA1) expression through immunofluorescence. The inflammation process was quantified using inflammatory/anti-inflammatory markers, e.g., tumor necrosis factor α (TNFα) and interleukin 10 (IL10) with ELISA. Peroxisome proliferator activated response γ (PPARγ) expression and activity were assessed with PCR and ELISA, respectively. The expression of microRNA 155 (miR-155) was examined using qPCR. Results: DCGTE at the above concentrations tended to reduce foam cell numbers, significantly inhibited lipid accumulation (p=0.000), reduced CD36 expression (p=0.000) and TNFα secretion (p=0.000) in Raw264.7 exposed to M-CSF 50ng/ml and oxLDL 50μg/ml. PPARγ expression (p=0.00) and activity (p=0.001), miR-155 relative expression (p=0.000), and IL10 production (p=0.000) also increased. Conclusion: DCGTE lowered foam cell numbers, possibly through attenuation of the inflammatory process and improvement of lipid/efflux mechanisms in M-CSF and oxLDL-stimulated Raw264.7 cells, via upregulation of PPARγ and miR-155. Our results suggest DCGTE may help prevent atherosclerosis-based diseases.

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Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis

Cited by 17 publications

References 53 publications

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Decaffeinated coffee and green tea extract inhibit foam cell atherosclerosis by lowering inflammation and improving cholesterol influx/efflux balance through upregulation of PPARγ and miR-155

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Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis

Cited by 17 publications

References 53 publications

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Punicalagin Regulates Key Processes Associated with Atherosclerosis in THP-1 Cellular Model

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates

Decaffeinated coffee and green tea extract inhibit foam cell atherosclerosis by lowering inflammation and improving cholesterol influx/efflux balance through upregulation of PPARγ and miR-155

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Product

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About

Modulating Lipoprotein Transcellular Transport and Atherosclerotic Plaque Formation in ApoE^–/– Mice via Nanoformulated Lipid–Methotrexate Conjugates