LRP5 deficiency down-regulates Wnt signalling and promotes aortic lipid infiltration in hypercholesterolaemic mice
Low-density lipoprotein receptor-related protein 5 (LRP5) is a member of the LDLR family that orchestrates cholesterol homoeostasis. The role of LRP5 and the canonical Wnt pathway in the vascular wall of dyslipidaemic animals remains unknown. In this study, we analysed the role of LRP5 and the Wnt s...
| Autores: | , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2015 |
| 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:p10502 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=10502 https://www.scopus.com/inward/record.uri?eid=2-s2.0-84925970823&doi=10.1111%2fjcmm.12396&partnerID=40&md5=b15a3aa3aa1246c88c29b6973c53dbcc |
| Access Level: | acceso abierto |
| Palabra clave: | Animalia Mus beta catenin cholesterol intake lipid low density lipoprotein receptor low density lipoprotein receptor related protein 5 Lrp1 protein, mouse Lrp2 protein, mouse Lrp5 protein, mouse megalin tumor suppressor protein adverse effects animal aorta blood C57BL mouse deficiency down regulation Dyslipidemias gene expression genetics hypercholesterolemia immunohistochemistry knockout mouse lipid diet macrophage metabolism reverse transcription polymerase chain reaction Wnt signaling pathway Animals Aorta beta Catenin Cholesterol, Dietary Diet, High-Fat Down-Regulation Gene Expression Hypercholesterolemia Immunohistochemistry Lipids Low Density Lipoprotein Receptor-Related Protein-2 Low Density Lipoprotein Receptor-Related Protein-5 Macrophages Mice, Inbred C57BL Mice, Knockout Receptors, LDL Reverse Transcriptase Polymerase Chain Reaction Tumor Suppressor Proteins Wnt Signaling Pathway |
| Sumario: | Low-density lipoprotein receptor-related protein 5 (LRP5) is a member of the LDLR family that orchestrates cholesterol homoeostasis. The role of LRP5 and the canonical Wnt pathway in the vascular wall of dyslipidaemic animals remains unknown. In this study, we analysed the role of LRP5 and the Wnt signalling pathway in mice fed a hypercholesterolaemic diet (HC) to trigger dyslipidaemia. We show that Lrp5-/- mice had larger aortic lipid infiltrations than wild-type mice, indicating a protective role for LRP5 in the vascular wall. Three members of the LDLR family, Lrp1, Vldlr and Lrp6, showed up-regulated gene expression levels in aortas of Lrp5-/- mice fed a hypercholesterolaemic diet. HC feeding in Lrp5-/- mice induced higher macrophage infiltration in the aortas and accumulation of inflammatory cytokines in blood. Wnt/ß-CATENIN signalling proteins were down-regulated in HC Lrp5-/- mice indicating that LRP5 regulates the activation of Wnt signalling in the vascular wall. In conclusion, our findings show that LRP5 and the canonical Wnt pathway down-regulation regulate the dyslipidaemic profile by promoting lipid and macrophage retention in the vessel wall and increasing leucocyte-driven systemic inflammation. © 2015 The Authors. |
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