E-MEXP-840 - Transcription profiling of aorta from mice underexpressing Fibulin-4 to investigate its role in elastic fibre assembly and cardio-vasuclar disease
Released on 1 January 2007, last updated on 27 March 2012
Extracellular elastic fibres apply structure and mechanical elasticity to organs such as large arteries, lungs and skin 1. Elastic fibres are assembled through polymerization of tropoelastin monomers and loss of elastin is associated with aneurysmal degeneration of the aorta 2. The Fibulins are a six-member protein family hypothesized to function as intermolecular bridges that stabilize the organization of extracellular matrix structures such as elastic fibres and basement membranes 3. Fibulin-4 is found in the medial layers of arteries and moderately expressed in heart valves 4. To examine a potential role of Fibulin-4 in elastic fibre assembly and cardio-vascular disease we generated a mouse model underexpressing Fibulin-4. To get insight into the underlying molecular pathways involved in aneurysm formation, we determined the aorta transcriptome of Fibulin-4R/R animals and identified biological processes that were significantly overrepresented including apoptosis and cell death as well as several novel gene targets implicated in the response to aortic failure. We conclude that decreased Fibulin-4 expression causes aberrant composition of the elastin layers in the aorta and valvular leaflets, resulting in aortic aneurysms and heart abnormalities.
transcription profiling by array, genetic modification, genotyping, organism status, physiological process
George A Garinis <firstname.lastname@example.org>, Jeroen Essers
Perturbations of Vascular Homeostasis and Aortic Valve Abnormalities in Fibulin-4 Deficient Mice. Katsuhiro Hanada, Marcel Vermeij, George A. Garinis, Monique C. de Waard, Maurice G.S. Kunen, Loretha Myers, Alex Maas, Dirk J. Duncker, Carel Meijers, Harry C. Dietz, Roland Kanaar, Jeroen Essers.