Regulator of calcineurin 1 mediates pathological vascular wall remodeling
Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved...
| Autores: | , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2011 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p10457 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10457 https://www.scopus.com/inward/record.uri?eid=2-s2.0-80555139632&doi=10.1084%2fjem.20110503&partnerID=40&md5=b6ef2ed1879503aada514d19927bf17d |
| Access Level: | acceso abierto |
| Palabra clave: | angiotensin II calcineurin calcineurin 1 CD3 antigen lentivirus vector protein Mac3 protein Rcan smooth muscle actin tubulin unclassified drug vimentin aneurysm animal cell animal experiment animal model animal tissue aorta wall article atherosclerosis cell migration controlled study gene genome analysis hypertension in vitro study in vivo study male mouse nonhuman priority journal rat Rcan1 gene restenosis signal transduction tunica media vascular disease vascular smooth muscle vascular wall remodeling Aneurysm Angiotensin II Animals Aorta Calcineurin Cell Movement Coronary Restenosis Cyclosporine Gene Expression Regulation Immunosuppressive Agents Intracellular Signaling Peptides and Proteins Male Mice Mice, Inbred C57BL Mice, Knockout Muscle Proteins Muscle, Smooth, Vascular NFATC Transcription Factors Rats Rats, Wistar Signal Transduction |
| Sumario: | Artery wall remodeling, a major feature of diseases such as hypertension, restenosis, atherosclerosis, and aneurysm, involves changes in the tunica media mass that reduce or increase the vessel lumen. The identification of molecules involved in vessel remodeling could aid the development of improved treatments for these pathologies. Angiotensin II (AngII) is a key effector of aortic wall remodeling that contributes to aneurysm formation and restenosis through incompletely defined signaling pathways. We show that AngII induces vascular smooth muscle cell (VSMC) migration and vessel remodeling in mouse models of restenosis and aneurysm. These effects were prevented by pharmacological inhibition of calcineurin (CN) or lentiviral delivery of CN-inhibitory peptides. Whole-genome analysis revealed >1,500 AngII-regulated genes in VSMCs, with just 11 of them requiring CN activation. Of these, the most sensitive to CN activation was regulator of CN 1 (Rcan1). Rcan1 was strongly activated by AngII in vitro and in vivo and was required for AngII-induced VSMC migration. Remarkably, Rcan1 -/- mice were resistant to AngII-induced aneurysm and restenosis. Our results indicate that aneurysm formation and restenosis share mechanistic elements and identify Rcan1 as a potential therapeutic target for prevention of aneurysm and restenosis progression. © 2011 Esteban et al. |
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