Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice
Atherogenesis is a long-term process that involves inflammatory response coupled with metabolic dysfunction. Foam cell formation and macrophage inflammatory response are two key events in atherogenesis. Adipocyte enhancer-binding protein 1 (AEBP1) has been shown to impede macrophage cholesterol effl...
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| مؤلفون آخرون: | , , , |
| التنسيق: | article |
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2011
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://hdl.handle.net/11073/25057 |
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| _version_ | 1864513437165420544 |
|---|---|
| author | Bogachev, Oleg |
| author2 | Majdalawieh, Amin Pan, Xuefang Zhang, Lei Ro, Hyo-Sung |
| author2_role | author author author author |
| author_facet | Bogachev, Oleg Majdalawieh, Amin Pan, Xuefang Zhang, Lei Ro, Hyo-Sung |
| author_role | author |
| dc.creator.none.fl_str_mv | Bogachev, Oleg Majdalawieh, Amin Pan, Xuefang Zhang, Lei Ro, Hyo-Sung |
| dc.date.none.fl_str_mv | 2011 2022-10-27T08:03:13Z 2022-10-27T08:03:13Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | Bogachev, O., Majdalawieh, A., Pan, X. et al. Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice. Mol Med 17, 1056–1064 (2011). https://doi.org/10.2119/molmed.2011.00141 1528-3658 http://hdl.handle.net/11073/25057 10.2119/molmed.2011.00141 |
| dc.language.none.fl_str_mv | en_US |
| dc.publisher.none.fl_str_mv | Springer Nature |
| dc.relation.none.fl_str_mv | https://doi.org/10.2119/molmed.2011.00141 |
| dc.subject.none.fl_str_mv | Adipocyte Enhancer-binding Protein (AEBP1) Low-density Lipoprotein Receptor (LDLR) ATP-binding Cassette A1 (ABCA1) ATP-binding Cassette G1 (ABCG1) Macrophage Inflammatory Responsiveness |
| dc.title.none.fl_str_mv | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| dc.type.none.fl_str_mv | Peer-Reviewed Published version info:eu-repo/semantics/publishedVersion info:eu-repo/semantics/article |
| description | Atherogenesis is a long-term process that involves inflammatory response coupled with metabolic dysfunction. Foam cell formation and macrophage inflammatory response are two key events in atherogenesis. Adipocyte enhancer-binding protein 1 (AEBP1) has been shown to impede macrophage cholesterol efflux, promoting foam cell formation, via peroxisome proliferator-activated receptor (PPAR)-γl and liver X receptor α (LXRα) downregulation. Moreover, AEBP1 has been shown to promote macrophage inflammatory responsiveness by inducing nuclear factor (NF)-κB activity via IκBα downregulation. Lipopolysaccharide (LPS)-induced suppression of pivotal macrophage cholesterol efflux mediators, leading to foam cell formation, has been shown to be mediated by AEBP₁. Herein, we showed that AEBP₁-transgenic mice (AEBP1ᵀᴳ) with macrophage-specific AEBP1 overexpression exhibit hyperlipidemia and develop atherosclerotic lesions in their proximal aortas. Consistently, ablation of AEBP₁ results in significant attenuation of atherosclerosis (males: 3.2-fold, P = 0.001 (en face)), 2.7-fold, P = 0.0004 (aortic roots); females: 2.1-fold, P = 0.0026 (en face), 1.7-fold, P = 0.0126 (aortic roots)) in the AEBP₁⁻′⁻/low-density lipoprotein receptor (LDLR)⁻′⁻ double-knockout (KO) mice. Bone marrow (BM) transplantation experiments further revealed that LDLR⁻′⁻ mice reconstituted with AEBP₁⁻′⁻/LDLR⁻′⁻ BM cells (LDLR⁻′⁻/KO-BM chimera) display significant reduction of atherosclerosis lesions (en face: 2.0-fold, P = 0.0268; aortic roots: 1.7-fold, P = 0.05) compared with control mice reconstituted with AEBP₁⁺′⁺/LDLR⁻′⁻ BM cells (LDLR⁻′⁻/WT-BM chimera). Furthermore, transplantation of AEBP1TG BM cells with the normal apolipoprotein E (ApoE) gene into ApoE⁻′⁻ mice (ApoE⁻′⁻/TG-BM chimera) leads to significant development of atherosclerosis (males: 2.5-fold, P = 0.0001 (en face), 4.7-fold, P = 0.0001 [aortic roots]; females: 1.8-fold, P = 0.0001 (en face), 3.0-fold, P = 0.0001 [aortic roots]) despite the restoration of ApoE expression. Macrophages from ApoE⁻′⁻/TG-BM chimeric mice express reduced levels of PPARγ₁, LXRα, ATP-binding cassette A₁ (ABCA₁) and ATP-binding cassette G₁ (ABCG₁) and increased levels of the inflammatory mediators interleukin (IL)-6 and tumor necrosis factor (TNF)-α compared with macrophages of control chimeric mice (ApoE⁻′⁻/NT-BM) that received AEBP₁ nontransgenic (AEBP₁ᴺᵀ) 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. |
| format | article |
| id | aus_03c1e1b13ef722bf4096c4a42e0641bb |
| identifier_str_mv | Bogachev, O., Majdalawieh, A., Pan, X. et al. Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice. Mol Med 17, 1056–1064 (2011). https://doi.org/10.2119/molmed.2011.00141 1528-3658 10.2119/molmed.2011.00141 |
| language_invalid_str_mv | en_US |
| network_acronym_str | aus |
| network_name_str | aus |
| oai_identifier_str | oai:repository.aus.edu:11073/25057 |
| publishDate | 2011 |
| publisher.none.fl_str_mv | Springer Nature |
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| spelling | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ MiceBogachev, OlegMajdalawieh, AminPan, XuefangZhang, LeiRo, Hyo-SungAdipocyte Enhancer-binding Protein (AEBP1)Low-density Lipoprotein Receptor (LDLR)ATP-binding Cassette A1 (ABCA1)ATP-binding Cassette G1 (ABCG1)Macrophage Inflammatory ResponsivenessAtherogenesis is a long-term process that involves inflammatory response coupled with metabolic dysfunction. Foam cell formation and macrophage inflammatory response are two key events in atherogenesis. Adipocyte enhancer-binding protein 1 (AEBP1) has been shown to impede macrophage cholesterol efflux, promoting foam cell formation, via peroxisome proliferator-activated receptor (PPAR)-γl and liver X receptor α (LXRα) downregulation. Moreover, AEBP1 has been shown to promote macrophage inflammatory responsiveness by inducing nuclear factor (NF)-κB activity via IκBα downregulation. Lipopolysaccharide (LPS)-induced suppression of pivotal macrophage cholesterol efflux mediators, leading to foam cell formation, has been shown to be mediated by AEBP₁. Herein, we showed that AEBP₁-transgenic mice (AEBP1ᵀᴳ) with macrophage-specific AEBP1 overexpression exhibit hyperlipidemia and develop atherosclerotic lesions in their proximal aortas. Consistently, ablation of AEBP₁ results in significant attenuation of atherosclerosis (males: 3.2-fold, P = 0.001 (en face)), 2.7-fold, P = 0.0004 (aortic roots); females: 2.1-fold, P = 0.0026 (en face), 1.7-fold, P = 0.0126 (aortic roots)) in the AEBP₁⁻′⁻/low-density lipoprotein receptor (LDLR)⁻′⁻ double-knockout (KO) mice. Bone marrow (BM) transplantation experiments further revealed that LDLR⁻′⁻ mice reconstituted with AEBP₁⁻′⁻/LDLR⁻′⁻ BM cells (LDLR⁻′⁻/KO-BM chimera) display significant reduction of atherosclerosis lesions (en face: 2.0-fold, P = 0.0268; aortic roots: 1.7-fold, P = 0.05) compared with control mice reconstituted with AEBP₁⁺′⁺/LDLR⁻′⁻ BM cells (LDLR⁻′⁻/WT-BM chimera). Furthermore, transplantation of AEBP1TG BM cells with the normal apolipoprotein E (ApoE) gene into ApoE⁻′⁻ mice (ApoE⁻′⁻/TG-BM chimera) leads to significant development of atherosclerosis (males: 2.5-fold, P = 0.0001 (en face), 4.7-fold, P = 0.0001 [aortic roots]; females: 1.8-fold, P = 0.0001 (en face), 3.0-fold, P = 0.0001 [aortic roots]) despite the restoration of ApoE expression. Macrophages from ApoE⁻′⁻/TG-BM chimeric mice express reduced levels of PPARγ₁, LXRα, ATP-binding cassette A₁ (ABCA₁) and ATP-binding cassette G₁ (ABCG₁) and increased levels of the inflammatory mediators interleukin (IL)-6 and tumor necrosis factor (TNF)-α compared with macrophages of control chimeric mice (ApoE⁻′⁻/NT-BM) that received AEBP₁ nontransgenic (AEBP₁ᴺᵀ) 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.Canadian Institutes of Health ResearchSpringer Nature2022-10-27T08:03:13Z2022-10-27T08:03:13Z2011Peer-ReviewedPublished versioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfBogachev, O., Majdalawieh, A., Pan, X. et al. Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice. Mol Med 17, 1056–1064 (2011). https://doi.org/10.2119/molmed.2011.001411528-3658http://hdl.handle.net/11073/2505710.2119/molmed.2011.00141en_UShttps://doi.org/10.2119/molmed.2011.00141oai:repository.aus.edu:11073/250572024-08-22T11:59:32Z |
| spellingShingle | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice Bogachev, Oleg Adipocyte Enhancer-binding Protein (AEBP1) Low-density Lipoprotein Receptor (LDLR) ATP-binding Cassette A1 (ABCA1) ATP-binding Cassette G1 (ABCG1) Macrophage Inflammatory Responsiveness |
| status_str | publishedVersion |
| title | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| title_full | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| title_fullStr | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| title_full_unstemmed | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| title_short | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| title_sort | Adipocyte Enhancer-Binding Protein 1 (AEBP1) (a Novel Macrophage Proinflammatory Mediator) Overexpression Promotes and Ablation Attenuates Atherosclerosis in ApoE⁻′⁻ and LDLR⁻′⁻ Mice |
| topic | Adipocyte Enhancer-binding Protein (AEBP1) Low-density Lipoprotein Receptor (LDLR) ATP-binding Cassette A1 (ABCA1) ATP-binding Cassette G1 (ABCG1) Macrophage Inflammatory Responsiveness |
| url | http://hdl.handle.net/11073/25057 |