on November 5, 2009
Published online before print November 5, 2009, doi: 10.1161/ATVBAHA.109.196725
Submitted on August 30, 2009
Accepted on September 29, 2009
Fibulin-2 and Fibulin-5 Cooperatively Function to Form the Internal Elastic Lamina and Protect From Vascular Injury
Shelby L. Chapman ;
From the Department of Molecular Biology (S.L.C., J.H., H.Y.), University of Texas Southwestern Medical Center, Dallas; the Department of Dermatology and Cutaneous Biology (F.-X. S., M.-L.C.), Thomas Jefferson University, Philadelphia, Pa; the Department of Anatomy and Cell Biology (E.C.D.), McGill University, Montreal, Quebec; and the Shriners Hospital for Children Research Center (T.S.), Portland, Ore. Current affiliation for F.-X.S.: Takara Bio Europe S.A.S., Saint-Germain-en-Laye, France.
* To whom correspondence should be addressed. E-mail: hiromi.yanagisawa{at}utsouthwestern.edu.
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.
Key words: internal elastic lamina • vascular remodeling • development • injury