| Neointima Formed by Arterial Smooth Muscle Cells Expressing Versican Variant V3 Is Resistant to Lipid and Macrophage Accumulation. | |
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MedLine Citation:
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PMID: 21441139 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Extracellular matrix (ECM) of neointima formed following angioplasty contains elevated levels of versican, loosely arranged collagen, and fragmented deposits of elastin, features associated with lipid and macrophage accumulation. ECM with a low versican content, compact structure, and increased elastic fiber content can be achieved by expression of versican variant V3, which lacks chondroitin sulfate glycosaminoglycans. We hypothesized that V3-expressing arterial smooth muscle cells (ASMC) can be used to form a neointima resistant to lipid and macrophage accumulation associated with hypercholesterolemia. METHODS AND RESULTS: ASMC transduced with V3 cDNA were seeded into ballooned rabbit carotid arteries, and animals were fed a chow diet for 4 weeks, followed by a cholesterol-enriched diet for 4 weeks, achieving plasma cholesterol levels of 20 to 25 mmol/L. V3 neointimae at 8 weeks were compact, multilayered, and elastin enriched. They were significantly thinner (57%) than control neointimae; contained significantly more elastin (118%), less collagen (22%), and less lipid (76%); and showed significantly reduced macrophage infiltration (85%). Mechanistic studies demonstrated that oxidized low-density lipoprotein stimulated the formation of this monocyte-binding ECM, which was inhibited in the presence of V3 expressing ASMC. CONCLUSIONS: These results demonstrate that expression of V3 in vessel wall creates an elastin-rich neointimal matrix that in the presence of hyperlipidemia is resistant to lipid deposition and macrophage accumulation. |
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Authors:
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Mervyn J Merrilees; Brent W Beaumont; Kathleen R Braun; Anita C Thomas; Inkyung Kang; Aleksander Hinek; Alberto Passi; Thomas N Wight |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-24 |
Journal Detail:
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Title: Arteriosclerosis, thrombosis, and vascular biology Volume: - ISSN: 1524-4636 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9505803 Medline TA: Arterioscler Thromb Vasc Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Anatomy with Radiology, School of Medical Sciences, University of Auckland, Auckland, New Zealand. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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