| Lipoprotein(a) promotes smooth muscle cell proliferation and dedifferentiation in atherosclerotic lesions of human apo(a) transgenic rabbits. | |
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MedLine Citation:
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PMID: 11786416 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Elevated plasma lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis. However, the mechanism underlying Lp(a) atherogenicity is unclear. Recently, we demonstrated that Lp(a) may potentially be proatherogenic in transgenic rabbits expressing human apolipoprotein(a) [apo(a)]. In this study, we further investigated atherosclerotic lesions of transgenic rabbits by morphometry and immunohistochemistry. On a cholesterol diet, human apo(a) transgenic rabbits had more extensive atherosclerotic lesions of the aorta, carotid artery, iliac artery, and coronary artery than did nontransgenic littermate rabbits as defined by increased intimal lesion area. Enhanced lesion development in transgenic rabbits was characterized by increased accumulation of smooth muscle cells, that was often associated with the Lp(a) deposition. To explore the possibility that Lp(a) may be involved in the smooth-muscle cell phenotypic modulation, we stained the lesions using a panel of monoclonal antibodies against smooth-muscle myosin heavy-chain isoforms (SM1, SM2, and SMemb) and basic transcriptional element binding protein-2 (BTEB2). We found that a large number of smooth muscle cells located in the apo(a)-containing areas of transgenic rabbits were positive for SMemb and BTEB2, suggesting that these smooth muscle cells were either immature or in the state of activation. In addition, transgenic rabbits showed delayed fibrinolytic activity accompanied by increased plasma plasminogen activator inhibitor-1. We conclude that Lp(a) may enhance the lesion development by mediating smooth muscle cell proliferation and dedifferentiation possibly because of impaired fibrinolytic activity. |
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Authors:
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Tomonaga Ichikawa; Hiroyuki Unoki; Huijun Sun; Hiroaki Shimoyamada; Santica Marcovina; Hisataka Shikama; Teruo Watanabe; Jianglin Fan |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: The American journal of pathology Volume: 160 ISSN: 0002-9440 ISO Abbreviation: Am. J. Pathol. Publication Date: 2002 Jan |
Date Detail:
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Created Date: 2002-01-11 Completed Date: 2002-07-05 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0370502 Medline TA: Am J Pathol Country: United States |
Other Details:
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Languages: eng Pagination: 227-36 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Genetically Modified / genetics Apolipoproteins A / genetics, pharmacology, physiology* Arteriosclerosis / blood, pathology*, physiopathology* Cell Differentiation / physiology Cell Division / physiology Female Fibrinolysis / drug effects Humans Immunohistochemistry / methods Lipids / blood Lipoprotein(a) / physiology* Lipoproteins / blood Male Muscle, Smooth, Vascular / pathology* Plasminogen / metabolism Plasminogen Activator Inhibitor 1 / blood Rabbits Staining and Labeling Transforming Growth Factor beta / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Apolipoproteins A; 0/Lipids; 0/Lipoprotein(a); 0/Lipoproteins; 0/Plasminogen Activator Inhibitor 1; 0/Transforming Growth Factor beta; 9001-91-6/Plasminogen |
| Comments/Corrections | |
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