Abstract |
Versican is an extracellular matrix (ECM) proteoglycan that is synthesized as multiple splice variants. In a recent study, we demonstrated that retroviral-mediated overexpression of the variant V3, which lacks chondroitin sulfate (CS) chains, altered arterial smooth muscle cell (ASMC) phenotype in short-term cell culture. We now report that V3-overexpressing ASMCs exhibit significantly increased expression of tropoelastin and increased formation of elastic fibers in long-term cell cultures. In addition, V3-overexpressing ASMCs seeded into ballooned rat carotid arteries continued to overexpress V3 and, at 4 weeks after seeding, produced a highly structured neointima significantly enriched in elastic fiber lamellae. In contrast to the hydrated, myxoid neointima produced by rounded or stellate vector-alone--transduced cells, V3-expressing cells produced a compact and highly ordered neointima, which contained elongated ASMCs that were arranged in parallel arrays and separated by densely packed collagen bundles and elastic fibers. These results indicate that a variant of versican is involved in elastic fiber assembly and may represent a novel therapeutic approach to facilitate the formation of elastic fibers.
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Authors | Mervyn J Merrilees, Joan M Lemire, Jens W Fischer, Michael G Kinsella, Kathleen R Braun, Alexander W Clowes, Thomas N Wight |
Journal | Circulation research
(Circ Res)
Vol. 90
Issue 4
Pg. 481-7
(Mar 08 2002)
ISSN: 1524-4571 [Electronic] United States |
PMID | 11884379
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Chondroitin Sulfate Proteoglycans
- Lectins, C-Type
- Protein Isoforms
- RNA, Messenger
- Tropoelastin
- Vcan protein, rat
- Versicans
- Elastin
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Topics |
- Animals
- Carotid Arteries
(cytology, physiology)
- Catheterization
- Cells, Cultured
- Chondroitin Sulfate Proteoglycans
(biosynthesis, genetics)
- Elastic Tissue
(metabolism, ultrastructure)
- Elastin
(metabolism, ultrastructure)
- Gene Expression
- Immunohistochemistry
- Lectins, C-Type
- Male
- Muscle, Smooth, Vascular
(cytology, metabolism, transplantation)
- Protein Isoforms
(biosynthesis, genetics)
- RNA, Messenger
(analysis, metabolism)
- Rats
- Rats, Inbred F344
- Retroviridae
(genetics)
- Time Factors
- Transduction, Genetic
- Tropoelastin
(biosynthesis, genetics)
- Tunica Intima
(cytology, metabolism, ultrastructure)
- Versicans
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