Show simple item record

dc.contributor.authorOller, Jorge 
dc.contributor.authorMendez-Barbero, Nerea 
dc.contributor.authorAlberca, Rut 
dc.contributor.authorLozano-Vidal, Noelia 
dc.contributor.authorIturri, Lizet Sandra
dc.contributor.authorJimenez-Borreguero, Luis J. 
dc.contributor.authorArroyo, Alicia G 
dc.contributor.authorCampanero, Miguel
dc.contributor.authorRedondo, Juan Miguel
dc.identifier.citationIMPRS Max Planck - Annual Retreat. 2015es_ES
dc.descriptionIMPRS Max Planck - Annual Retreat. Bad Nauheim, junio 2015es_ES
dc.description.abstractAneurysms involving the aortic root and the ascending aorta leading to dissections are the major diseases affecting the aorta and a common cause of premature deaths ranking as high as the XXth cause of death in developed countries. The major constituent of the vessel wall is the extracellular matrix (ECM). It forms part of the basic structure of blood vessels and provides structural and mechanical support through elasticity, stiffness, and intercellular communication. Changes in ECM proteins expression, assembly, cross-linking, and degradation can trigger physiological pathological conditions in the vascular wall, including atherosclerosis, aneurysms, stenosis and hypertension (Hellenthal et al. 2009). Mutations in genes which encode ECM proteins which affects mechanical properties of tissues are present in some inherited connective tissue disorders such as Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), vascular type of Ehlers-Danlos syndrome (EDS-IV), and familial forms of non-syndromic thoracic aneurysm and dissection (FTAAD) (Hoffjan 2012, Van Laer et al. 2014). TGFβ signaling pathway is overactivated in both syndromic and non-syndromic aortic diseases, TGFβ signaling pathway suggesting that it plays a pivotal role in these diseases. The ADAMTS family of of extracellular metalloproteinases degrade proteoglycans and therefore have the potential to modify tissue architecture and function (Stanton 2011). Recently, different works have involved the families, ADAMTS and ADAMTSL (Adamts-like) in fibril microfiber formation thus suggesting a role of these genes in the regulation of TGFβ signalling (Hoffjan et al 2012). Different mutations in ADAMTS/ADAMTSL superfamily members has been described as causative of connective tissue disorders without aortic phenotype (Le Goff et al. 2011). Adamts1 is widely expressed in aortic endothelial and VSMCs during development and in adulthood (Thai et al. 2002; Luque et. al. 2003) and under pathological vascular remodeling in (Jönsson-Rylanderand et al. 2005) and thoracic aneurysm (Pen et. al. 2013). However the role of this metalloproteinase in the vascular wall is poorly understood. Here, we show the potential role of Adamts1 in vascular wall homeostasis using two different approaches, a genetic model of Adamts1 deficient mice and a knocking-down model in aorta using short-interference RNA (siRNA) expressing lentiviruses. Both models, Adamts1 deficient mice and knocking-down present some vascular features that resembles aortic disorders, such as aortic ectasia, fibrosis, proteoglycan accumulation, elastin breaks, TGFb hyperactivation. These phenotype was exacerbated by AngII infusion. These data supports that Adamts1 is essential for vascular integrity in homeostasis and remodelinges_ES
dc.relation.isreferencedbyHellenthal, F. A. et al. Nat. Rev. Cardiol. (2009)es_ES
dc.relation.isreferencedbyHoffjan et al. Mol Syndromol (2011)es_ES
dc.relation.isreferencedbyVan Laer et al. Exp Med Biol (2014)es_ES
dc.relation.isreferencedbyJonsson-Rylander AC Arterioscler. Thromb. Vasc. Biol. (2005)es_ES
dc.relation.isreferencedbyShindo et al. J Clin Invest (2000)es_ES
dc.relation.isreferencedbyThai et al. Mech Dev (2002)es_ES
dc.relation.isreferencedbyLuque et al. J Biol Chem (2003)es_ES
dc.titleAdamts1 in vascular homeostasis and remodellinges_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.repisalud.orgCNICCNIC::Grupos de investigación::Regulación Génica en Remodelado Vascular e Inflamaciónes_ES

Files in this item

Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional