title: Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells.
abstract: Atherosclerosis is a chronic inflammatory cardiovascular disease that is responsible of high mortality worldwide. Evidence indicates that maladaptive autoimmune responses in the arterial wall play critical roles in the process of atherosclerosis. Cortistatin is a neuropeptide expressed in the vascular system and atherosclerotic plaques that regulates vascular calcification and neointimal formation, and inhibits inflammation in different experimental models of autoimmune diseases. Its role in inflammatory cardiovascular disorders is largely unexplored. The aim of this study is to investigate the potential therapeutic effects of cortistatin in two well-established preclinical models of atherosclerosis, and the molecular and cellular mechanisms involved. Systemic treatment with cortistatin reduced the number and size of atherosclerotic plaques in carotid artery, heart, aortic arch and aorta in acute and chronic atherosclerosis induced in apolipoprotein E-deficient mice fed a high-lipid diet. This effect was exerted at multiple levels. Cortistatin reduced Th1/Th17-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and lymphoid organs. Moreover, cortistatin reduced the capacity of endothelial cells to bind and recruit immune cells to the plaque and impaired the formation of foam cells by enhancing cholesterol efflux from macrophages. Cortistatin emerges as a new candidate for the treatment of the clinical manifestations of atherosclerosis.
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Virginia
authors.initials: V
authors.lastname: Delgado-Maroto
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Benitez
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Forte-Lago
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Morell
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Maganto-Garcia
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Luciana
authors.initials: L
authors.lastname: Souza-Moreira
authors.affiliation: Department of Pathology, School of Medicine, University of Granada, Granada, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: O'Valle
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.|Medical Sciences, University of Castilla-La Mancha, Ciudad Real, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Duran-Prado
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Lichtman
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Gonzalez-Rey
authors.affiliation: Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Delgado
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D005260:Female; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism; D006949:Hyperlipidemias / Q000150:complications* / Q000235:genetics; D051379:Mice; D000074085:Mice, Knockout, ApoE; D009479:Neuropeptides / Q000008:administration & dosage* / Q000494:pharmacology; D058226:Plaque, Atherosclerotic / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D009479:Neuropeptides; C099323:cortistatin