Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration.
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.
Spencer
Jeffrey A
JA
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Hacker
Shelby L
SL
Davis
Elaine C
EC
Mecham
Robert P
RP
Knutsen
Russ H
RH
Li
Dean Y
DY
Gerard
Robert D
RD
Richardson
James A
JA
Olson
Eric N
EN
Yanagisawa
Hiromi
H
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
D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D011994:Recombinant Proteins