Background: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome. Methods: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial ‘ShockOmics’ (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects. Results: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation. Conclusions: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients. Clinical trial registration: NCT02141607.
Proteolysis in septic shock patients : plasma peptidomic patterns are associated with mortality / J. Bauzá-Martinez, F. Aletti, B.B. Pinto, V. Ribas, M.A. Odena, R. Díaz, E.R. Medina, R. Ferrer, E.B. Kistler, G. Tedeschi, G.W. Schmid-Schönbein, A. Herpain, K. Bendjelid, E. de Oliveira. - In: BRITISH JOURNAL OF ANAESTHESIA. - ISSN 0007-0912. - 121:5(2018 Nov), pp. 1065-1074.
|Titolo:||Proteolysis in septic shock patients : plasma peptidomic patterns are associated with mortality|
|Parole Chiave:||in-hospital mortality; mass spectrometry; peptidomics; proteolysis; septic shock; Anesthesiology and Pain Medicine|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||nov-2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bja.2018.05.072|
|Appare nelle tipologie:||01 - Articolo su periodico|