title: A major role for RCAN1 in atherosclerosis progression.
abstract: 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.
authors.affiliation: Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Méndez-Barbero
authors.forename: Vanesa
authors.initials: V
authors.lastname: Esteban
authors.forename: Silvia
authors.initials: S
authors.lastname: Villahoz
authors.forename: Amelia
authors.initials: A
authors.lastname: Escolano
authors.forename: Katia
authors.initials: K
authors.lastname: Urso
authors.forename: Arantzazu
authors.initials: A
authors.lastname: Alfranca
authors.forename: Cristina
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Susana A
authors.initials: SA
authors.lastname: Sánchez
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Osawa
authors.forename: Vicente
authors.initials: V
authors.lastname: Andrés
authors.forename: José
authors.initials: J
authors.lastname: Martínez-González
authors.forename: Takashi
authors.initials: T
authors.lastname: Minami
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Redondo
authors.forename: Miguel R
authors.initials: MR
authors.lastname: Campanero
mesh_terms: D000783:Aneurysm / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005487:Foam Cells / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D002135:Calcium-Binding Proteins; C511512:DSCR1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008077:Lipoproteins, LDL; D009124:Muscle Proteins; C099252:oxidized low density lipoprotein
keywords: RCAN1; atherosclerosis; hypercholesterolemia; inflammation; macrophage