Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury

Shelby L. Chapman, F. X. Sicot, Elaine C. Davis, Jianbin Huang, Takako Sasaki, Mon Li Chu, Hiromi Yanagisawa

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

OBJECTIVE-: Recent findings on the role of fibulin-5 (Fbln5) have provided substantial progress in understanding the molecular mechanism of elastic fiber assembly in vitro. However, little is known about differential roles of fibulins in the elastogenesis of blood vessels. Here, we generated double knockout mice for Fbln5 and Fbln2 (termed DKO) and examined the role of fibulins-2 and-5 in development and injury response of the blood vessel wall. METHODS AND RESULTS-: Fibulin-2 is distinctly located in the subendothelial matrix, whereas fibulin-5 is observed throughout the vessel wall. All of the elastic laminae, including the internal elastic lamina (IEL), were severely disorganized in DKO mice, which was not observed in single knockout mice for Fbln2 or Fbln5. Furthermore, DKO vessels displayed upregulation of vascular adhesion molecules, tissue factor expression, and thrombus formation with marked dilation and thinning of the vessel wall after carotid artery ligation-injury. CONCLUSIONS-: Fibulin-2 and fibulin-5 cooperatively function to form the IEL during postnatal development by directing the assembly of elastic fibers, and are responsible for maintenance of the adult vessel wall after injury. The DKO mouse will serve as a unique animal model to test the effect of vessel integrity during various pathological insults.

Original languageEnglish (US)
Pages (from-to)68-74
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • Development
  • Injury
  • Internal elastic lamina
  • Vascular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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