Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease

Maguire, Eithne Margaret; Pearce, Stuart; Xiao, Qingzhong

doi:10.1016/j.vph.2018.08.002

Cited by 265 publications

(207 citation statements)

References 240 publications

Supporting

Mentioning

205

Contrasting

Unclassified

Order By: Relevance

“…IL‐1 β is known to regulate adhesion molecules, such as VCAM‐1, and promote leukocyte adherence to endothelial cells and migration, which increase monocytes adhesion and infiltration into the vascular wall, leading to atherosclerosis . CCL2, known as monocyte chemoattractant protein‐1 (MCP‐1), plays essential roles in monocyte recruitment toward atherosclerotic arteries, and knock down of CCL2 may reduce atherosclerotic lesion size . IL‐6, combining with soluble IL‐6 receptor, triggers up‐regulation of chemokines and ICAM‐1 expression in endothelial cells, which together permit the recruitment and transmigration of leukocytes in atherosclerosis plaque .…”

Section: Discussionmentioning

confidence: 99%

“…[21,22] CCL2, known as monocyte chemoattractant protein-1 (MCP-1), plays essential roles in monocyte recruitment toward atherosclerotic arteries, and knock down of CCL2 may reduce atherosclerotic lesion size. [23] IL-6, combining with soluble IL-6 receptor, triggers upregulation of chemokines and ICAM-1 expression in endothelial cells, which together permit the recruitment and transmigration of leukocytes in atherosclerosis plaque. [24] Among these inflammatory cytokines, the secretion of TNF and IL-6 can be mediated by cholesterol induced activation of ERK1/2 (known as MAKP1/3), JNK1 (known as MAPK8) in macrophage in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Integrating Network Pharmacology and Component Analysis Study on Anti‐Atherosclerotic Mechanisms of Total Flavonoids of Engelhardia roxburghiana Leaves in Mice

Wei

Zhang

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

Engelhardia roxburghiana Wall. leaves are widely used to develop herbal teas in southeast of China due to medicinal use for diabetes mellitus and hyperlipidemia. Studies have demonstrated that the total flavonoids of E. roxburghiana leaves (TFER) exhibited regulatory effects on blood glucose and lipids. To clarify the active ingredients of TFER and their targets in treating atherosclerosis, the present study integrated chemical analysis, network pharmacology analysis and animal experimental studies. Firstly, high performance liquid chromatography‐mass spectrometry/mass spectrometry (HPLC/MS/MS) was utilized to identify components of TFER. Then, active ingredients were screened by oral bioavailability (OB) and drug‐likeness (DL) index. Thirdly, network was constructed to predict major targets of active ingredients against atherosclerosis. Finally, to verify parts of predicted signaling, Apoe−/− mice were used to develop atherosclerosis. Atherosclerotic plaques in aorta were evaluated by echocardiography. Then, serum lipids, target genes expressions in thoracic aorta were determined by qRT‐PCR and ELISA methods. Chemical analysis revealed 10 components in TFER sample, 7 of which acted as active ingredients, including naringenin, kaempferol, quercetin, isoengeletin, engeletin, astilbin and quercitrin. KEGG pathway analysis highly enriched in some inflammatory signalings, including NF‐κB signaling, Toll‐like receptor signaling and TNF signaling. The animal studies indicated that TFER reduced atherosclerotic plaques size in aorta and significantly decreased the serum lipids, down‐regulated NF‐κB signaling by decreasing mRNA level of NF‐κB p65 subunit, TNF‐α and VCAM‐1, as well as IL‐1β expressions in thoracic aorta, eventually alleviating atherosclerosis progression, which was in consistent with our prediction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrating Network Pharmacology and Component Analysis Study on Anti‐Atherosclerotic Mechanisms of Total Flavonoids of Engelhardia roxburghiana Leaves in Mice

Wei

Zhang

et al. 2020

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

“…Although the detailed mechanisms of this disease are not yet fully defined, it has been believed that regulation of cholesterol metabolism and the inflammatory response by lipid‐laden macrophages are critical steps in the initiation and progression of atherosclerosis . Several lines of evidence suggest that inhibition of foam cell formation retards the progression of atherosclerosis in experimental animal models . The formation of foam cells is primarily caused by uncontrolled uptake of oxidized low‐density lipoprotein (oxLDL) or impaired cholesterol efflux in macrophages, which result in excessive oxLDL‐derived lipid accumulation inside macrophages .…”

Section: Introductionmentioning

confidence: 99%

“…17,18 Several lines of evidence suggest that inhibition of foam cell formation retards the progression of atherosclerosis in experimental animal models. [19][20][21] The formation of foam cells is primarily caused by uncontrolled uptake of oxidized low-density lipoprotein (oxLDL) or impaired cholesterol efflux in macrophages, which result in excessive oxLDL-derived lipid accumulation inside macrophages. 19,22 Scavenger receptors (SRs) class A SR (SR-A) and CD36 are responsible for internalization of oxLDL.…”

mentioning

confidence: 99%

“…[19][20][21] The formation of foam cells is primarily caused by uncontrolled uptake of oxidized low-density lipoprotein (oxLDL) or impaired cholesterol efflux in macrophages, which result in excessive oxLDL-derived lipid accumulation inside macrophages. 19,22 Scavenger receptors (SRs) class A SR (SR-A) and CD36 are responsible for internalization of oxLDL. 23,24 By contrast, the efflux of accumulated cholesterol in macrophages is mediated through reverse cholesterol transporters (RCTs) including SR-BI and the ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1).…”

mentioning

confidence: 99%

See 1 more Smart Citation

The phosphatase activity of soluble epoxide hydrolase regulates ATP‐binding cassette transporter‐A1‐dependent cholesterol efflux

Lien

Chen

Lee

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

The contribution of soluble epoxide hydrolase (sEH) to atherosclerosis has been well defined. However, less is understood about the role of sEH and its underlying mechanism in the cholesterol metabolism of macrophages. The expression of sEH protein was increased in atherosclerotic aortas of apolipoprotein E‐deficient mice, primarily in macrophage foam cells. Oxidized low‐density lipoprotein (oxLDL) increased sEH expression in macrophages. Genetic deletion of sEH (sEH−/−) in macrophages markedly exacerbated oxLDL‐induced lipid accumulation and decreased the expression of ATP‐binding cassette transporters‐A1 (ABCA1) and apolipoprotein AI‐dependent cholesterol efflux following oxLDL treatment. The down‐regulation of ABCA1 in sEH−/− macrophages was due to an increase in the turnover rate of ABCA1 protein but not in mRNA transcription. Inhibition of phosphatase activity, but not hydrolase activity, of sEH decreased ABCA1 expression and cholesterol efflux following oxLDL challenge, which resulted in increased cholesterol accumulation. Additionally, oxLDL increased the phosphatase activity, promoted the sEH‐ABCA1 complex formation and decreased the phosphorylated level of ABCA1 at threonine residues. Overexpression of phosphatase domain of sEH abrogated the oxLDL‐induced ABCA1 phosphorylation and further increased ABCA1 expression and cholesterol efflux, leading to the attenuation of oxLDL‐induced cholesterol accumulation. Our findings suggest that the phosphatase domain of sEH plays a crucial role in the cholesterol metabolism of macrophages.

show abstract

Biomimetic Macrophage Membrane and Lipidated Peptide Hybrid Nanovesicles for Atherosclerosis Therapy

Guo

Miao

Wang

et al. 2022

Adv Funct Materials

View full text Add to dashboard Cite

Atherosclerosis is the underlying cause for cardiovascular disease. Current pharmacotherapies are limited by the inadequate targeting and insufficient treatment. Herein, inspired by the interaction of macro phage and lipoprotein as a typical hallmark of atherosclerosis, hybrid nano vesicles (MLPNVs) are designed by fusion of antiinflammatory M2phenotype macrophage membranes and lipidated peptide (DOPEpp HBSP) to mimic the binding manner of celllipoprotein for atherosclerotic treatment. Through hybridization of M2 macrophage membranes and lipidated peptide film, MLPNVs facilitate the inflammatory cell inter nalization at atherosclerotic site, and sequester the proinflammatory cytokines to suppress local inflammation. Moreover, MLPNVs exhibit a matrix metalloprotease 2 (MMP2)responsive release of the peptide HBSP in plaques, leading to the restoration of dysfunctional endothelial cells. In the ApoE −/− mice with atherosclerosis, simvastatinloaded MLPNVs provide comprehensive treatment by inherent inflammation suppression, endothelial repair, and cholesterol efflux capacities, resulting in athero sclerotic plaques regression. Through closely mimicking physiological cues, this biomimetic hybrid nano vesicle platform provides a potential strategy for antiatherosclerotic therapy.

show abstract

Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease

Cited by 265 publications

References 240 publications

Integrating Network Pharmacology and Component Analysis Study on Anti‐Atherosclerotic Mechanisms of Total Flavonoids of Engelhardia roxburghiana Leaves in Mice

Integrating Network Pharmacology and Component Analysis Study on Anti‐Atherosclerotic Mechanisms of Total Flavonoids of Engelhardia roxburghiana Leaves in Mice

The phosphatase activity of soluble epoxide hydrolase regulates ATP‐binding cassette transporter‐A1‐dependent cholesterol efflux

Biomimetic Macrophage Membrane and Lipidated Peptide Hybrid Nanovesicles for Atherosclerosis Therapy

Contact Info

Product

Resources

About