Ac-hE-18A-NH2, a novel dual-domain apolipoprotein mimetic peptide, inhibits apoptosis in macrophages by promoting cholesterol efflux

Xie, Qiang; Li, Feng; Zhao, Shui‐Ping

doi:10.3892/mmr.2014.2056

Cited by 4 publications

(5 citation statements)

References 30 publications

(25 reference statements)

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“…Furthermore, in RAW264.7 macrophage-derived foam cells, the activation of autophagy ameliorates cholesterol accumulation through an ABCA1dependent pathway that mediates cholesterol efflux. Meanwhile, it is well documented that the accumulation of intracellular cholesterol is also crucial to induce macrophage apoptosis in vivo and in vitro [34,35]. Similar to our previous study [14], we found that autophagy activation is protective against luteolin-induced apoptosis in ox-LDL-induced macrophages.…”

Section: Discussionsupporting

confidence: 89%

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy

Zhang

Wang

et al. 2016

Cell Physiol Biochem

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Background: Our previous studies demonstrated that luteolin, which is rich in flavones, has various biological properties and can exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. However, its effect on ox-LDL-induced macrophage lipid accumulation and apoptosis has not been revealed. Aims: This study aimed to explore the role of luteolin in ox-LDL-induced macrophage-derived foam cell formation and apoptosis and to delineate the underlying mechanism. Methods: Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (50 µg/ml) for 24 h and then pretreated with 25 µM luteolin for another 24 h. The effects of luteolin on lipid accumulation in RAW264.7 cells induced by ox-LDL were assayed using Oil red O staining and high performance liquid chromatography (HPLC). Apoptosis was confirmed by acridine orange/ethidium bromide (AO/EB) staining, flow cytometric analysis and the TUNEL assay. Immunofluorescence, Western blot and monodansylcadaverine (MDC) staining analyses were then used to further investigate the molecular mechanisms by which luteolin protects macrophages from ox-LDL-induced foam cell formation and apoptosis. 3-Methyladenine (3-MA), an autophagy inhibitor, was used as a positive control. Results: Treatment with 25 µM luteolin not only significantly attenuated ox-LDL-induced macrophage lipid accumulation but also decreased the apoptotic rate of RAW264.7 cells, the number of TUNEL-positive macrophages and the expression of Bax, Bak, cleaved caspase-9 and cleaved caspase-3. In addition, luteolin pretreatment significantly increased autophagosome formation and Beclin-1 activity, thus increasing the ratio of LC3-II/LC3-I. Moreover, these effects were abolished by 3-MA. Conclusions: Taken together, these results highlight that luteolin treatment attenuates foam cell formation and macrophage apoptosis by promoting autophagy and provide new insights into the molecular mechanism of luteolin and its therapeutic potential in the treatment of atherosclerosis.

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Section: Discussionsupporting

confidence: 89%

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy

Zhang

Wang

et al. 2016

Cell Physiol Biochem

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“…Concentrations of intracellular cholesterol were determined by kits as previously reported [ 28 ]. Protein pellets were solubilized in 1 M NaOH (Sinopharm Chemical Reagent Co., Ltd, Shanghai, China), and the protein concentration was determined using a BCA Protein Assay (Thermo Fisher Scientific Inc., Rockford, IL, USA).…”

Section: Methodsmentioning

confidence: 99%

Spiromastixones Inhibit Foam Cell Formation via Regulation of Cholesterol Efflux and Uptake in RAW264.7 Macrophages

Chen

Liu

et al. 2015

Marine Drugs

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Bioassay-guided evaluation shows that a deep sea-derived fungus, Spiromastix sp. MCCC 3A00308, possesses lipid-lowering activity. Chromatographic separation of a culture broth resulted in the isolation of 15 known depsidone-based analogues, labeled spiromastixones A–O (1–15). Each of these compounds was tested for its ability to inhibit oxidized low-density lipoprotein (oxLDL)-induced foam cell formation in RAW264.7 macrophages. Spiromastixones 6–8 and 12–14 significantly decreased oxLDL-induced lipid over-accumulation, reduced cell surface area, and reduced intracellular cholesterol concentration. Of these compounds, spiromastixones 6 and 14 exerted the strongest inhibitory effects. Spiromastixones 6 and 14 dramatically inhibited cholesterol uptake and stimulated cholesterol efflux to apolipoprotein A1 (ApoA1) and high-density lipoprotein (HDL) in RAW264.7 macrophages. Mechanistic investigation indicated that spiromastixones 6, 7, 12 and 14 significantly up-regulated the mRNA levels of ATP-binding cassette sub-family A1 (ABCA1) and down-regulated those of scavenger receptor CD36, while the transcription of ATP-binding cassette sub-family A1 (ABCG1) and proliferator-activated receptor gamma (PPARγ) were selectively up-regulated by 6 and 14. A transactivation reporter assay revealed that spiromastixones 6 and 14 remarkably enhanced the transcriptional activity of PPARγ. These results suggest that spiromastixones inhibit foam cell formation through upregulation of PPARγ and ABCA1/G1 and downregulation of CD36, indicating that spiromastixones 6 and 14 are promising lead compounds for further development as anti-atherogenic agents.

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“…The 18A peptide was one of the first mimetic peptides designed and evaluated for confirming the amphipathic helix hypothesis ( Table 1 ). Originally designed to characterize and study the behavior of amphipathic helices in nanodisc assembly [ 179 , 180 ], the 18A peptide also demonstrated anti-inflammatory properties [ 181 , 182 ]. For example, 18A was able to rapidly assemble with phospholipids into nanodiscs, solubilizing unilamellar vesicles and confirming the amphipathic helix hypothesis.…”

Section: The Era Of Hdl Mimetic Nanoparticles: Replenishing Hdl Quali...mentioning

confidence: 99%

“…They were shown to efflux cholesterol from macrophages and prevent monocyte adhesion to primary human endothelial cells. N and C terminal modifications with acetyl and amide groups were shown to enhance the lipophilicity and helicity of the peptide [ 181 ]. It was later renamed as 2F due to two phenyl alanine residues.…”

Section: The Era Of Hdl Mimetic Nanoparticles: Replenishing Hdl Quali...mentioning

confidence: 99%

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

Rani

Marsche

2023

Pharmaceutics

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High-density lipoproteins (HDL) are complex endogenous nanoparticles involved in important functions such as reverse cholesterol transport and immunomodulatory activities, ensuring metabolic homeostasis and vascular health. The ability of HDL to interact with a plethora of immune cells and structural cells places it in the center of numerous disease pathophysiologies. However, inflammatory dysregulation can lead to pathogenic remodeling and post-translational modification of HDL, rendering HDL dysfunctional or even pro-inflammatory. Monocytes and macrophages play a critical role in mediating vascular inflammation, such as in coronary artery disease (CAD). The fact that HDL nanoparticles have potent anti-inflammatory effects on mononuclear phagocytes has opened new avenues for the development of nanotherapeutics to restore vascular integrity. HDL infusion therapies are being developed to improve the physiological functions of HDL and to quantitatively restore or increase the native HDL pool. The components and design of HDL-based nanoparticles have evolved significantly since their initial introduction with highly anticipated results in an ongoing phase III clinical trial in subjects with acute coronary syndrome. The understanding of mechanisms involved in HDL-based synthetic nanotherapeutics is critical to their design, therapeutic potential and effectiveness. In this review, we provide a current update on HDL-ApoA-I mimetic nanotherapeutics, highlighting the scope of treating vascular diseases by targeting monocytes and macrophages.

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Ac-hE-18A-NH2, a novel dual-domain apolipoprotein mimetic peptide, inhibits apoptosis in macrophages by promoting cholesterol efflux

Cited by 4 publications

References 30 publications

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy

Spiromastixones Inhibit Foam Cell Formation via Regulation of Cholesterol Efflux and Uptake in RAW264.7 Macrophages

A Current Update on the Role of HDL-Based Nanomedicine in Targeting Macrophages in Cardiovascular Disease

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