Survivin and caspases serum protein levels and survivin variants mRNA expression in sepsis.
Marianna MiliarakiPanagiotis BriassoulisStavroula IliaAikaterini PolonifiMarina MantzouraniEfrossini BriassouliKonstantinos VardasSerafim NanasAikaterini PistikiMaria TheodorakopoulouTheonymfi TavladakiAnna Maria SpanakiEumorfia KondiliHelen DimitriouSotirios TsiodrasDimitrios GeorgopoulosApostolos ArmaganidisGeorge DaikosGeorge BriassoulisPublished in: Scientific reports (2021)
Sepsis is a dysregulated host response to infection related to devastating outcomes. Recently, interest has been shifted towards apoptotic and antiapoptotic pathobiology. Apoptosis is executed through the activation of caspases regulated by a number of antiapoptotic proteins, such as survivin. The survivin and caspases' responses to sepsis have not yet been elucidated. This is a multicenter prospective observational study concerning patients with sepsis (n = 107) compared to patients with traumatic systemic inflammatory response syndrome (SIRS) (n = 75) and to healthy controls (n = 89). The expression of survivin was quantified through real-time quantitative polymerase chain reaction for the different survivin splice variants (wild type-WT, ΔEx3, 2B, 3B) in peripheral blood leukocytes. The apoptotic or antiapoptotic tendency was specified by measuring survivin-WT, caspase-3, and -9 serum protein concentrations through enzyme-linked immunosorbent assay. The survivin-WT, -2B, -ΔΕx3 mRNA, survivin protein, and caspases showed an escalated increase in SIRS and sepsis, whereas survivin-3B was repressed in sepsis (p < 0.05). Survivin correlated with IL-8 and caspase-9 (p < 0.01). For discriminating sepsis, caspase-9 achieved the best receiver operating characteristic curve (AUROC) of 0.95. In predicting mortality, caspase-9 and survivin protein achieved an AUROC of 0.70. In conclusion, specific apoptotic and antiapoptotic pathways might represent attractive targets for future research in sepsis.
Keyphrases
- cell death
- septic shock
- acute kidney injury
- intensive care unit
- inflammatory response
- peripheral blood
- binding protein
- type diabetes
- oxidative stress
- high resolution
- cell cycle arrest
- coronary artery disease
- high throughput
- endoplasmic reticulum stress
- wild type
- dna methylation
- anti inflammatory
- insulin resistance
- mass spectrometry
- case report
- cardiovascular events
- single cell
- signaling pathway