title: Fibulin-2 and fibulin-5 cooperatively function to form the internal elastic lamina and protect from vascular injury.
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.
  
  
  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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9148. hiromi.yanagisawa@utsouthwestern.edu.
authors.forename: Shelby L
authors.initials: SL
authors.lastname: Chapman
authors.forename: F-X
authors.initials: FX
authors.lastname: Sicot
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Davis
authors.forename: Jianbin
authors.initials: J
authors.lastname: Huang
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Mon-Li
authors.initials: ML
authors.lastname: Chu
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yanagisawa
mesh_terms: D000818:Animals; D001011:Aorta / Q000254:growth & development / Q000378:metabolism; D001018:Aortic Diseases / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002339:Carotid Arteries / Q000254:growth & development / Q000378:metabolism*; D020212:Carotid Artery Injuries / Q000378:metabolism*; D004195:Disease Models, Animal; D004548:Elasticity; D004730:Endothelium, Vascular / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D014333:Tropoelastin / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C120769:Fbln5 protein, mouse; D011994:Recombinant Proteins; D014333:Tropoelastin; D019010:Vascular Cell Adhesion Molecule-1; C084612:fibulin 2; D018799:Intercellular Adhesion Molecule-1