title: Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration.
abstract: Fibulin (fbln)-5 is an elastin-binding protein required for assembly and organization of elastic fibers. To examine the potential role of fbln-5 in vascular remodeling and neointima formation, we induced vascular injury by carotid artery ligation in fbln-5(-/-) mice. Mutant mice displayed an exaggerated vascular remodeling response that was accompanied by severe neointima formation with thickened adventitia. These abnormalities were not observed in elastin(+/-) mice that exhibited a comparable reduction of vessel extensibility to fbln-5(-/-) mice. Thus, the severe remodeling response could not be attributed to altered extensibility of the vessel wall alone. Vascular smooth muscle cells cultured from fbln-5(-/-) mice displayed enhanced proliferative and migratory responses to mitogenic stimulation relative to wild-type cells, and these responses were inhibited by overexpression of fbln-5. These findings demonstrate the importance of the elastic laminae in vascular injury, and reveal an unexpected role of fbln-5 as an inhibitor of vascular smooth muscle cell proliferation and migration.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Spencer
authors.forename: Shelby L
authors.initials: SL
authors.lastname: Hacker
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Davis
authors.forename: Robert P
authors.initials: RP
authors.lastname: Mecham
authors.forename: Russ H
authors.initials: RH
authors.lastname: Knutsen
authors.forename: Dean Y
authors.initials: DY
authors.lastname: Li
authors.forename: Robert D
authors.initials: RD
authors.lastname: Gerard
authors.forename: James A
authors.initials: JA
authors.lastname: Richardson
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanagisawa
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D004548:Elasticity; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011994:Recombinant Proteins; D017539:Tunica Intima / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D011994:Recombinant Proteins