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.
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.
Merrilees
Mervyn J
MJ
Department of Anatomy with Radiology, The University of Auckland, Auckland, New Zealand.
Lemire
Joan M
JM
Fischer
Jens W
JW
Kinsella
Michael G
MG
Braun
Kathleen R
KR
Clowes
Alexander W
AW
Wight
Thomas N
TN
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
D011508:Chondroitin Sulfate Proteoglycans; D037181:Lectins, C-Type; D020033:Protein Isoforms; D012333:RNA, Messenger; D014333:Tropoelastin; C508324:Vcan protein, rat; D053675:Versicans; D004549:Elastin