| Selective reduction in the sphingomyelin content of atherogenic lipoproteins inhibits their retention in murine aortas and the subsequent development of atherosclerosis. | |
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MedLine Citation:
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PMID: 20814016 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: We used the sphingomyelin (SM) synthase 2 (Sms2) gene knockout (KO) approach to test our hypothesis that selectively decreasing plasma lipoprotein SM can play an important role in preventing atherosclerosis. METHODS AND RESULTS: The sphingolipid de novo synthesis pathway is considered a promising target for pharmacological intervention in atherosclerosis. However, its potential is hampered because the substance's atherogenic mechanism is not completely understood. We prepared Sms2 and apolipoprotein E (Apoe) double-KO mice. They showed a significant decrease in plasma lipoprotein SM levels (35%, P<0.01) and a significant increase in ceramide and dihydroceramide levels (87.5% and 27%, respectively; P<0.01) but no significant changes in other tested sphingolipids, cholesterol, and triglyceride. Non-high-density lipoproteins from the double-KO mice showed a reduction of SM, but not cholesterol, and displayed less tendency toward aortic sphingomyelinase-mediated lipoprotein aggregation in vitro and retention in aortas in vivo when compared with controls. More important, at the age of 19 weeks, Sms2 KO/Apoe KO mice showed a significant reduction in atherosclerotic lesions of the aortic arch and root (52%, P<0.01) compared with controls. The Sms2 KO/Apoe KO brachiocephalic artery contained significantly less SM, ceramide, free cholesterol, and cholesteryl ester (35%, 32%, 58%, and 60%, respectively; P<0.01) than that of the Apoe KO brachiocephalic artery. CONCLUSIONS: Decreasing plasma SM levels through decreasing SMS2 activity could become a promising treatment for atherosclerosis. |
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Authors:
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Yifan Fan; Fujun Shi; Jing Liu; Jibin Dong; Hai H Bui; David A Peake; Ming-Shang Kuo; Guoqing Cao; Xian-Cheng Jiang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-09-02 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: 30 ISSN: 1524-4636 ISO Abbreviation: Arterioscler. Thromb. Vasc. Biol. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-21 Completed Date: 2010-12-20 Revised Date: - |
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: 2114-20 Citation Subset: IM |
Affiliation:
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Department of Cardiology, Renmin Hospotal, Wuhan University, Wuhan, China. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Aorta / metabolism*, physiopathology Atherosclerosis / genetics, metabolism*, prevention & control Lipoproteins / metabolism* Mice Sphingomyelins / metabolism* Transferases (Other Substituted Phosphate Groups) / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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HL094319/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipoproteins; 0/Sphingomyelins; EC 2.7.8.-/Transferases (Other Substituted Phosphate Groups); EC 2.7.8.27/sphingomyelin synthase 2, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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