title: The neuropeptide cortistatin attenuates experimental autoimmune myocarditis via inhibition of cardiomyogenic T cell-driven inflammatory responses.
abstract: Myocarditis is an inflammatory and autoimmune cardiovascular disease that causes dilated myocardiopathy and is responsible for high morbidity and mortality worldwide. Cortistatin is a neuropeptide produced by neurons and cells of the immune and vascular systems. Besides its action in locomotor activity and sleep, cortistatin inhibits inflammation in different experimental models of autoimmune diseases. However, its role in inflammatory cardiovascular disorders is unexplored. Here, we investigated the therapeutic effects of cortistatin in a well-established preclinical model of experimental autoimmune myocarditis (EAM).
  
  
  
  We induced EAM by immunization with a fragment of cardiac myosin in susceptible Balb/c mice. Cortistatin was administered i.p. starting 7, 11 or 15 days after EAM induction. At day 21, we evaluated heart hypertrophy, myocardial injury, cardiac inflammatory infiltration and levels of serum and cardiac inflammatory cytokines, cortistatin and autoantibodies. We determined proliferation and cytokine production by heart draining lymph node cells in response to cardiac myosin restimulation.
  
  
  
  Systemic injection of cortistatin during the effector phase of the disease significantly reduced its prevalence and signs of heart hypertrophy and injury (decreased the levels of brain natriuretic peptide) and impaired myocardial inflammatory cell infiltration. This effect was accompanied by a reduction in self-antigen-specific T-cell responses in lymph nodes and in the levels of cardiomyogenic antibodies and inflammatory cytokines in serum and myocardium. Finally, we found a positive correlation between cardiac and systemic cortistatin levels and EAM severity.
  
  
  
  Cortistatin emerges as a new candidate to treat inflammatory dilated cardiomyopathy.
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: Clara P
authors.initials: CP
authors.lastname: Falo
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: Norma
authors.initials: N
authors.lastname: Adan
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, MA, 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: Gema
authors.initials: G
authors.lastname: Robledo
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: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 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; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D008198:Lymph Nodes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009205:Myocarditis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
chemical_list: D016207:Cytokines; D009479:Neuropeptides; C099323:cortistatin