Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE−/− and LDLR−/− Mice

Bogachev, Oleg; Majdalawieh, Amin F.; Pan, Xuefang; Zhang, Lei; Ro, Hyo‐Sung

doi:10.2119/molmed.2011.00141

Cited by 31 publications

(20 citation statements)

References 41 publications

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“…Lipopolysaccharide has been suggested to suppress cholesterol efflux via induction of AEBP1 expression [46]. It has been reported that AEBP1-transgenic mice with macrophage-specific AEBP1 overexpression exhibit hyperlipidemia and develop atherosclerotic lesions in their proximal aortas, whereas ablation of AEBP1 results in significant attenuation of atherosclerosis [47]. More recently, Huang et al [48] reported that berberine attenuated ox-LDL accumulation and foam cell formation in phorbol 12-myristate 13-acetate-induced macrophages through inhibition of AEBP1.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Yuan

Fu²,

Ren³

et al. 2015

Cardiology

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Objective: High levels of soluble CD40 ligand (sCD40L) in the circulation have been suggested as an important indicator of cardiovascular diseases such as atherosclerosis and acute coronary syndromes. In the present study, we explored the role of sCD40L in the formation of foam cells. Methods: Lipid deposition and foam cell formation was measured by high-performance liquid chromatography and Nile Red staining, respectively. Gene expressions were detected by quantitative real-time PCR and Western blot analysis. The interaction between CD40 and sCD40L were blocked by CD40 small interfering RNA or anti-CD40 antibody. Results: sCD40L significantly increased lipid deposition and foam cell formation associated with upregulation of scavenger receptor type A and CD36. Additionally, sCD40L increased adipocyte enhancer-binding protein 1 and cholesterol efflux, and activated NF-κB in macrophages. sCD40L promoted foam cell formation via CD40 ligation and disruption of the ligation between CD40 and CD40L either by small interfering RNA or by a blocking anti-CD40 antibody apparently inhibiting foam cell formation in response to sCD40L. Conclusion: Our data suggests a novel insight into the role of sCD40L in foam cell formation during atherosclerosis, which further confirms the importance of sCD40L in atherosclerosis and as a target for the treatment of this disease.

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Section: Discussionmentioning

confidence: 99%

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Yuan

Fu²,

Ren³

et al. 2015

Cardiology

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“…AEBP1 overexpression in AAA results in the activation of NF-κB/p65 and the consequent upregulation of inflammatory cytokines IL-1β, IL-6, TNFα, and MCP-1, as well as MMP2 and MMP-9, matrix metalloproteinases (MMPs) [25]. In addition, modulation of AEBP1 expression has been implicated in other processes and conditions such as adipogenesis [2,5,6,11,26,27], mammary gland development [28][29][30], macrophage cholesterol homeostasis [8,12,31], inflammation [8,25,28,32], and atherosclerosis [32].…”

Section: Introductionmentioning

confidence: 99%

AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways

Majdalawieh

Massri

2020

Journal of Oncology

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Adipocyte enhancer-binding protein 1 (AEBP1) is a transcriptional repressor involved in the regulation of critical biological processes including adipogenesis, mammary gland development, inflammation, macrophage cholesterol homeostasis, and atherogenesis. Several years ago, we first reported the ability of AEBP1 to exert a positive control over the canonical NF-κB pathway. Indeed, AEBP1 positively regulates NF-κB activity via its direct interaction with IκBα, a key NF-κB inhibitor. AEBP1 overexpression results in uncontrollable activation of NF-κB, which may have severe pathogenic outcomes. Recently, the regulatory relationship between AEBP1 and NF-κB pathway has been of great interest to many researchers primarily due to the implication of NF-κB signaling in critical cellular processes such as inflammation and cancer. Since constitutive activation of NF-κB is widely implicated in carcinogenesis, AEBP1 overexpression is associated with tumor development and progression. Recent studies sought to explore the effects of the overexpression of AEBP1, as a potential oncogene, in different types of cancer. In this review, we analyze the effects of AEBP1 overexpression in a variety of malignancies (e.g., breast cancer, glioblastoma, bladder cancer, gastric cancer, colorectal cancer, ovarian cancer, and skin cancer), with a specific focus on the AEBP1-mediated control over the canonical NF-κB pathway. We also underscore the ability of AEBP1 to regulate crucial cancer-related events like cell proliferation and apoptosis in light of other key pathways (e.g., PI3K-Akt, sonic hedgehog (Shh), p53, parthanatos (PARP-1), and PTEN). Identifying AEBP1 as a potential biomarker for cancer prognosis may lead to a novel therapeutic target for the prevention and/or treatment of various types of cancer.

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“…In addition, full‐length AEBP1 is predominantly secreted from smooth muscle cells to the extracellular matrix of mesenchymal cells , while the short isoform of AEBP1 appears to reside in the cytoplasm or nuclei and regulate intracellular signaling . Diverse physiological functions of AEBP1 have previously been reported including the activation of inflammatory processes in macrophages by activating nuclear factor kappa B (NF‐κB) , inhibition of peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) and liver X receptor alpha (LXRα) , regulation of adipogenesis via phosphatase and tensin homolog deleted from chromosome 10 (PTEN) in preadipocytes , abdominal wall development and lung fibrosis . In mice, the short isoform of Aebp1 rather than the full‐length isoform seems to have the activity of inflammatory processes in macrophages .…”

Section: Introductionmentioning

confidence: 99%

Association of adipocyte enhancer‐binding protein 1 with Alzheimer's disease pathology in human hippocampi

et al. 2017

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Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-jB pathway in macrophages and regulates adipogenesis in preadipocytes. Up-regulation of AEBP1 in the hippocampi of patients with Alzheimer's disease (AD) has been revealed by microarray analyses of autopsied brains from the Japanese general population (the Hisayama study). In this study, we compared the expression patterns of AEBP1 in normal and AD brains, including in the hippocampus, using immunohistochemistry. The subjects were 24 AD cases and 52 non-AD cases. Brain specimens were immunostained with antibodies against AEBP1, tau protein, amyloid b protein, NF-jB, GFAP and Iba-1. In normal brains, AEBP1 immunoreactivity mainly localized to the perikarya of hippocampal pyramidal neurons, and its expression was elevated in the pyramidal neurons and some astrocytes in AD hippocampi. Although AEBP1 immunoreactivity was almost absent in neurons containing neurofibrillary tangles, AEBP1 was highly expressed in neurons with pretangles and in the tau-immunopositive, dystrophic neurites of senile plaques. Nuclear localization of NF-jB was also observed in certain AEBP1-positive neurons in AD cases.Comparison of AD and non-AD cases suggested a positive correlation between the expression level of AEBP1 and the degree of amyloid b pathology. These findings imply that AEBP1 protein has a role in the progression of AD pathology.

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Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE−/− and LDLR−/− Mice

Abstract: /NT-BM ) that received AEBP1 nontransgenic (AEBP1 NT ) BM cells. Our in vivo experimental data strongly suggest that macrophage AEBP1 plays critical regulatory roles in atherogenesis, and it may serve as a potential therapeutic target for the prevention or treatment of atherosclerosis.

Cited by 31 publications

References 41 publications

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

Soluble CD40 Ligand Promotes Macrophage Foam Cell Formation in the Etiology of Atherosclerosis

AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways

Association of adipocyte enhancer‐binding protein 1 with Alzheimer's disease pathology in human hippocampi

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