A major role for RCAN1 in atherosclerosis progression
Atherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1...
| Autores: | , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| 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:p10057 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10057 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84897005459&doi=10.1002%2femmm.201302842&partnerID=40&md5=b94df75edb77dea7d5c7cf4d702f2277 |
| Access Level: | acceso abierto |
| Palabra clave: | CD36 antigen gelatinase A gelatinase B interleukin 10 mannose receptor oxidized low density lipoprotein protein protein rcan 1 unclassified drug animal experiment animal model animal tissue antigen expression antigen presentation aorta arch aorta sinus aorta valve disease article ascending aorta atherogenesis atheroma atherosclerosis atherosclerotic plaque chemotaxis comparative study controlled study coronary artery disease course disease severity endothelium cell gene inactivation genotype hematopoietic cell hematopoietic stem cell human human tissue internal mammary artery lipid storage macrophage macrophage migration mouse nonhuman peritoneum macrophage phenotype priority journal protein expression smooth muscle fiber upregulation vascular smooth muscle hypercholesterolemia inflammation RCAN1 Aneurysm Animals Antigens, CD36 Apolipoproteins E Atherosclerosis Bone Marrow Cells Bone Marrow Transplan |
| Sumario: | Atherosclerosis is a complex inflammatory disease involving extensive vascular vessel remodelling and migration of vascular cells. As RCAN1 is implicated in cell migration, we investigated its contribution to atherosclerosis. We show RCAN1 induction in atherosclerotic human and mouse tissues. Rcan1 was expressed in lesional macrophages, endothelial cells and vascular smooth muscle cells and was induced by treatment of these cells with oxidized LDLs (oxLDLs). Rcan1 regulates CD36 expression and its genetic inactivation reduced atherosclerosis extension and severity in Apoe-/- mice. This effect was mechanistically linked to diminished oxLDL uptake, resistance to oxLDL-mediated inhibition of macrophage migration and increased lesional IL-10 and mannose receptor expression. Moreover, Apoe-/-Rcan1-/- macrophages expressed higher-than-Apoe-/- levels of anti-inflammatory markers. We previously showed that Rcan1 mediates aneurysm development and that its expression is not required in haematopoietic cells for this process. However, transplantation of Apoe-/-Rcan1-/- bone-marrow (BM) cells into Apoe-/- recipients confers atherosclerosis resistance. Our data define a major role for haematopoietic Rcan1 in atherosclerosis and suggest that therapies aimed at inhibiting RCAN1 expression or function might significantly reduce atherosclerosis burden. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO. |
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