title: Dermcidin: a skeletal muscle myokine modulating cardiomyocyte survival and infarct size after coronary artery ligation.
abstract: OBJECTIVE
  Coronary artery disease is the leading cause of death in western countries, and its association with lower extremity peripheral artery disease (LE-PAD) represents an independent predictor of worse outcome. However, the molecular mechanisms underlying these effects are currently unknown.
  
  
  RESULTS
  To investigate these processes, we used in vitro approaches and several mouse models: (i) unilateral limb ischaemia by left common femoral artery ligation [peripheral ischaemia (PI), n = 38]; (ii) myocardial infarction by permanent ligation of the left descending coronary artery (MI, n = 40); (iii) MI after 5 weeks of limb ischaemia (PI + MI, n = 44); (iv) sham operation (SHAM, n = 20). Compared with MI, PI + MI hearts were characterized by a significant increase in cardiomyocyte apoptosis, larger infarct areas, and decreased cardiac function. By using a proteomic approach, we identified a ≅ 8 kDa circulating peptide, Dermcidin (DCD), secreted by ischaemic skeletal muscles, enhancing cardiomyocytes apoptosis under hypoxic conditions and infarct size after permanent coronary artery ligation. siRNA interference experiments to reduce DCD circulating levels significantly reduced infarct size and ameliorated cardiac function after MI.
  
  
  CONCLUSIONS
  Our data demonstrate that chronic limb ischaemia activates detrimental pathways in the ischaemic heart through humoral mechanisms of remote organ crosstalk. Thus, DCD may represent a novel important myokine modulating cardiomyocyte survival and function.
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy espogiov@unina.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Gabriele Giacomo
authors.initials: GG
authors.lastname: Schiattarella
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Perrino
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Cattaneo
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy Department of Medicine, Duke University Medical Center, Durham, USA.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Pironti
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Franzone
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Gargiulo
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Magliulo
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Serino
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carotenuto
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Sannino
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ilardi
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Fernando
authors.initials: F
authors.lastname: Scudiero
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Linda
authors.initials: L
authors.lastname: Brevetti
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Oliveti
authors.affiliation: Montevergine Clinic, Mercogliano, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Giugliano
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Del Giudice
authors.affiliation: Department of Medicine and Surgery, University of Salerno, Naples, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Ciccarelli
authors.affiliation: Proteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Renzone
authors.affiliation: Proteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council, Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.affiliation: Department of Molecular Medicine and Medical Biotechnologies/CEINGE-Advanced Biotechnology, Federico II University, Naples, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Zambrano
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, Naples 80131, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000601:surgery*; D054805:Dermcidins / Q000378:metabolism*; D004195:Disease Models, Animal; D008026:Ligation / Q000379:methods; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000601:surgery; D009203:Myocardial Infarction / Q000378:metabolism / Q000601:surgery*; D017202:Myocardial Ischemia / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*
chemical_list: D054805:Dermcidins
keywords: Apoptosis; Cardiomyocytes; Dermicidin; Myocardial ischemia; Peripheral artery disease