Altered vascular remodeling in fibulin-5-deficient mice reveals a role of fibulin-5 in smooth muscle cell proliferation and migration

Jeffrey A. Spencer, Shelby L. Hacker, Elaine C. Davis, Robert P. Mecham, Russ H. Knutsen, Dean Y. Li, Robert D. Gerard, James A. Richardson, Eric N. Olson, Hiromi Yanagisawa

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2946-2951
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number8
DOIs
StatePublished - Feb 22 2005

Keywords

  • Elastic fibers
  • Elastin
  • Extracellular matrix
  • Neointima

ASJC Scopus subject areas

  • General

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