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Platelet-derived exosomes from septic shock patients induce myocardial dysfunction.

Azevedo LC, Janiszewski M, Pontieri V, Pedro Mde A, Bassi E, Tucci PJ, Laurindo FR - Crit Care (2007)

Bottom Line: 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.This negative inotropic effect was fully reversible upon withdrawal of exosomes.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

Introduction: 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.

Conclusion: 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.

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Exosomes from patients with septic shock. Electron micrograph of exosomes isolated from the plasma of patients with sepsis, showing round particles with diameters ranging from 50 to 150 nm. Magnification, × 41,000.
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Figure 1: Exosomes from patients with septic shock. Electron micrograph of exosomes isolated from the plasma of patients with sepsis, showing round particles with diameters ranging from 50 to 150 nm. Magnification, × 41,000.

Mentions: Figure 1 depicts transmission electron micrography of exosomes from septic patients. Exosomes were identified as round particles with diameters ranging from 50 to 150 nm, consistent with previous reports [13], with no deposit of electron-dense material (negative stain). Some larger particles can also be seen in the preparation, probably corresponding to microparticles derived from plasma membranes.


Platelet-derived exosomes from septic shock patients induce myocardial dysfunction.

Azevedo LC, Janiszewski M, Pontieri V, Pedro Mde A, Bassi E, Tucci PJ, Laurindo FR - Crit Care (2007)

Exosomes from patients with septic shock. Electron micrograph of exosomes isolated from the plasma of patients with sepsis, showing round particles with diameters ranging from 50 to 150 nm. Magnification, × 41,000.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2246209&req=5

Figure 1: Exosomes from patients with septic shock. Electron micrograph of exosomes isolated from the plasma of patients with sepsis, showing round particles with diameters ranging from 50 to 150 nm. Magnification, × 41,000.
Mentions: Figure 1 depicts transmission electron micrography of exosomes from septic patients. Exosomes were identified as round particles with diameters ranging from 50 to 150 nm, consistent with previous reports [13], with no deposit of electron-dense material (negative stain). Some larger particles can also be seen in the preparation, probably corresponding to microparticles derived from plasma membranes.

Bottom Line: 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.This negative inotropic effect was fully reversible upon withdrawal of exosomes.

View Article: PubMed Central - HTML - PubMed

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

ABSTRACT

Introduction: 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.

Conclusion: 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.

Show MeSH
Related in: MedlinePlus