title: The synthetic antimicrobial peptide 19-2.5 attenuates septic cardiomyopathy and prevents down-regulation of SERCA2 in polymicrobial sepsis.
abstract: An impairment of cardiac function is a key feature of the cardiovascular failure associated with sepsis. Although there is some evidence that suppression of sarcoplasmic reticulum Ca2+-ATP-ase (SERCA2) contributes to septic cardiomyopathy, it is not known whether prevention of the down-regulation of SERCA2 improves outcome in sepsis. Thus, we investigated whether the administration of the synthetic antimicrobial peptide Pep2.5 may attenuate the cardiac dysfunction in murine polymicrobial sepsis through regulating SERCA2 expression. We show here for the first time that the infusion of Pep2.5 reduces the impaired systolic and diastolic contractility and improves the survival time in polymicrobial sepsis. Preservation of cardiac function in sepsis by Pep2.5 is associated with prevention of the activation of NF-κB and activation of the Akt/eNOS survival pathways. Most notably, Pep2.5 prevented the down-regulation of SERCA2 expression in a) murine heart samples obtained from mice with sepsis and b) in cardiomyocytes exposed to serum from septic shock patients. Thus, we speculate that Pep2.5 may be able to prevent down-regulation of cardiac SERCA2 expression in patients with sepsis, which, in turn, may improve cardiac function and outcome in these patients.
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany.|The William Harvey Research Institute, Barts &The London School of Medicine &Dentistry, Queen Mary University of London, London, UK.
authors.forename: Lukas
authors.initials: L
authors.lastname: Martin
authors.affiliation: Department of Orthopaedic Trauma, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Klemens
authors.initials: K
authors.lastname: Horst
authors.affiliation: Department of Drug Science &Technology, University of Turin, Turin, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Chiazza
authors.affiliation: Department of Drug Science &Technology, University of Turin, Turin, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Oggero
authors.affiliation: Department of Drug Science &Technology, University of Turin, Turin, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Collino
authors.affiliation: Division of Biophysics, Forschungszentrum Borstel, Borstel, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: Department of Orthopaedic Trauma, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Hildebrand
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Marx
authors.affiliation: The William Harvey Research Institute, Barts &The London School of Medicine &Dentistry, Queen Mary University of London, London, UK.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiemermann
authors.affiliation: Department of Intensive Care and Intermediate Care, University Hospital RWTH Aachen, Aachen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Schuerholz
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000096:biosynthesis*; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
chemical_list: D023181:Antimicrobial Cationic Peptides; D016328:NF-kappa B; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506947:Atp2a2 protein, mouse