title: Platelet-derived exosomes from septic shock patients induce myocardial dysfunction.
abstract: BACKGROUND
  Mechanisms underlying inotropic failure in septic shock are incompletely understood. We previously identified the presence of exosomes in the plasma of septic shock patients. These exosomes are released mainly by platelets, produce superoxide, and induce apoptosis in vascular cells by a redox-dependent pathway. We hypothesized that circulating platelet-derived exosomes could contribute to inotropic dysfunction of sepsis.
  
  
  METHODS
  We collected blood samples from 55 patients with septic shock and 12 healthy volunteers for exosome separation. Exosomes from septic patients and healthy individuals were investigated concerning their myocardial depressant effect in isolated heart and papillary muscle preparations.
  
  
  RESULTS
  Exosomes from the plasma of septic patients significantly decreased positive and negative derivatives of left ventricular pressure in isolated rabbit hearts or developed tension and its first positive derivative in papillary muscles. Exosomes from healthy individuals decreased these variables non-significantly. In hearts from rabbits previously exposed to endotoxin, septic exosomes decreased positive and negative derivatives of ventricular pressure. This negative inotropic effect was fully reversible upon withdrawal of exosomes. Nitric oxide (NO) production from exosomes derived from septic shock patients was demonstrated by fluorescence. Also, there was an increase in myocardial nitrate content after exposure to septic exosomes.
  
  
  CONCLUSIONS
  Circulating platelet-derived exosomes from septic patients induced myocardial dysfunction in isolated heart and papillary muscle preparations, a phenomenon enhanced by previous in vivo exposure to lipopolysaccharide. The generation of NO by septic exosomes and the increased myocardial nitrate content after incubation with exosomes from septic patients suggest an NO-dependent mechanism that may contribute to myocardial dysfunction of sepsis.
authors.affiliation: Emergency Medicine Research Laboratory, University of São Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar 255, sala 5023, São Paulo, Brazil. lucianoazevedo@uol.com.br
authors.forename: Luciano Cesar Pontes
authors.initials: LC
authors.lastname: Azevedo
authors.forename: Mariano
authors.initials: M
authors.lastname: Janiszewski
authors.forename: Vera
authors.initials: V
authors.lastname: Pontieri
authors.forename: Marcelo de Almeida
authors.initials: Mde A
authors.lastname: Pedro
authors.forename: Estevão
authors.initials: E
authors.lastname: Bassi
authors.forename: Paulo José Ferreira
authors.initials: PJ
authors.lastname: Tucci
authors.forename: Francisco Rafael Martins
authors.initials: FR
authors.lastname: Laurindo
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000009:adverse effects / Q000097:blood; D001792:Blood Platelets / Q000473:pathology*; D009202:Cardiomyopathies / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D002462:Cell Membrane / Q000378:metabolism*; D022162:Cytoplasmic Vesicles / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000097:blood; D012772:Shock, Septic / Q000097:blood* / Q000150:complications
chemical_list: D001324:Autoantigens; D017382:Reactive Oxygen Species