title: [Elastin and microfibrils in vascular development and                                     ageing: complementary or opposite roles?].
abstract: Large arteries allow the vascular system to be more than a simple route in which the blood circulates within the organism. The elastic fibers present in the wall endow these vessels with elasticity and are responsible for the smoothing of the blood pressure and flow, which are delivered discontinuously by the heart. This function is very important to ensure appropriate hemodynamics. Elastic fibers are composed of elastin (90%) and fibrillin-rich microfibrils (10%) which provide the vessels with elasticity and are also signals able to bind to relatively specific cell membrane receptors. Stimulation of the high affinity elastin receptor by elastin peptides or tropoelastin--the elastin precursor--triggers an increase in intracellular free calcium in vascular cells, especially endothelial cells, associated with attachment, migration or proliferation. Similar effects of the stimulation of endothelial cells by microfibrils or fibrillin-1 fragments, which bind to integrins, have been demonstrated. This dual function--mechanical and in signaling--makes the elastic fibers an important actor of the development and ageing processes taking place in blood vessels. An alteration of the elastin (Eln) or fibrillin (Fbn) gene products leads to severe genetic pathologies of the cardiovascular system, such as supravalvular aortic stenosis, or Williams Beuren syndrome--in which elastin deficiency induces aortic stenoses--or Marfan syndrome, in which on the contrary fibrillin-1 deficiency promotes the appearance of aortic aneurysms. Genetically-engineered mouse models of these pathologies (such as Eln+/- mice and Fbn-1+/mgΔ mice, Eln+/-Fbn-1+/- mice) have permitted a better understanding of the pathogenesis of these syndromes. In particular, it has been shown that elastin and fibrillin-1 roles can be complementary in some aspects, while they can be opposed in some other situations. For instance, the double heterozygosity in elastin and fibrillin-1 leads to increased arterial wall stress--compared to the level induced by one of these two deficiencies alone--while the decrease in diameter induced by Eln deficiency is partly compensated by an additional deficiency in Fbn-1. Also, it is now clear that early modifications of elastin or fibrillin-1 availability can alter the normal signaling action of these proteins and lead to long term modifications of the vascular physiology and ageing processes.
authors: Laboratoire Hypoxie: Physiopathologie Cardiovasculaire et Respiratoire (HP2), INSERM U 1042, Université Joseph Fourier, Bâtiment Jean Roget, Facultés de Médecine et de Pharmacie, Domaine de La Merci, 38706 La Tronche, France.
authors: Wassim
authors: W
authors: Fhayli
authors: Zeinab
authors: Z
authors: Ghandour
authors: Boubacar
authors: B
authors: Mariko
authors: Mylène
authors: M
authors: Pezet
authors: Gilles
authors: G
authors: Faury
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000254:growth & development* / Q000378:metabolism; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D004549:Elastin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000071838:Fibrillin-1; D000071837:Fibrillins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D020894:Microfibrils / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D054392:Adipokines
chemical_list: D004549:Elastin; D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines; C000605724:Fbn1 protein, mouse