title: Retrovirally mediated overexpression of versican v3 by arterial smooth muscle cells induces tropoelastin synthesis and elastic fiber formation in vitro and in neointima after vascular injury.
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.
authors.affiliation: Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand.
authors.forename: Mervyn J
authors.initials: MJ
authors.lastname: Merrilees
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lemire
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Michael G
authors.initials: MG
authors.lastname: Kinsella
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Braun
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Clowes
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000166:cytology / Q000502:physiology; D002404:Catheterization; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis* / Q000235:genetics; D004547:Elastic Tissue / Q000378:metabolism* / Q000648:ultrastructure; D004549:Elastin / Q000378:metabolism / Q000648:ultrastructure; D015870:Gene Expression; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic; D014333:Tropoelastin / Q000096:biosynthesis* / Q000235:genetics; D017539:Tunica Intima / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D053675:Versicans
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D020033:Protein Isoforms; D012333:RNA, Messenger; D014333:Tropoelastin; C508324:Vcan protein, rat; D053675:Versicans; D004549:Elastin