| Apoptosis signal-regulating kinase 1 deficiency accelerates hyperlipidemia-induced atheromatous plaques via suppression of macrophage apoptosis. | |
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MedLine Citation:
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PMID: 21527753 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: The pathogenic role of macrophage apoptosis in atherosclerosis is still debatable, but it is considered to be a suppressor of plaque progression in early stages but a promoter of plaque necrosis in advanced stages. Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase that plays a pivotal role in stress-induced apoptosis. In the current study, we investigated the functions of ASK1 in hyperlipidemia-induced atherosclerosis. METHODS AND RESULTS: We generated ASK1 and apolipoprotein E (apoE) double-knockout mice (ASK1(-/-)/apoE(-/-)) and analyzed atherosclerosis in ASK1(-/-)/apoE(-/-) mice fed a high-cholesterol diet for 12 weeks. ASK1(-/-)/apoE(-/-) mice had accelerated hyperlipidemia-induced atherosclerosis, which was characterized by less apoptosis of macrophages and fewer necrotic areas, and more macrophages and elastolysis compared with apoE(-/-) mice. Bone marrow transplantation from ASK1(-/-) or wild-type to apoE(-/-) mice confirmed the above observation that the recipient mice of ASK1(-/-) donors had more pronounced hyperlipidemia-induced atherosclerosis than recipient mice of wild-type donors. CONCLUSIONS: These findings suggest that ASK1 suppresses hyperlipidemia-induced atherosclerosis via increased macrophage apoptosis and that ASK1 may cause pronounced plaque vulnerability via necrotic core development. |
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Authors:
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Sohsuke Yamada; Yan Ding; Akihide Tanimoto; Ke-Yong Wang; Xin Guo; Zhi Li; Takashi Tasaki; Atsunori Nabesima; Yoshitaka Murata; Shohei Shimajiri; Kimitoshi Kohno; Hidenori Ichijo; Yasuyuki Sasaguri |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-04-28 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 31 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-16 Completed Date: 2011-08-19 Revised Date: 2011-11-02 |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1555-64 Citation Subset: IM |
Affiliation:
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Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. yasu3219@med.uoeh-u.ac.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta / enzymology*, pathology Apolipoproteins E / deficiency, genetics Apoptosis* Body Weight Bone Marrow Transplantation Cholesterol, Dietary Disease Models, Animal Elastic Tissue / metabolism Foam Cells / enzymology*, pathology Hyperlipidemias / enzymology*, etiology, genetics, pathology Immunohistochemistry Lipoproteins / blood MAP Kinase Kinase Kinase 5 / deficiency*, genetics Macrophages, Peritoneal / enzymology*, pathology Male Mice Mice, Inbred C57BL Mice, Knockout Necrosis Plaque, Atherosclerotic / enzymology*, etiology, genetics, pathology Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins E; 0/Cholesterol, Dietary; 0/Lipoproteins; EC 2.7.11.25/MAP Kinase Kinase Kinase 5; EC 2.7.11.25/Map3k5 protein, mouse |
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