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Circulating Endothelial Cells From Septic Shock Patients Convert to Fibroblasts Are Associated With the Resuscitation Fluid Dose and Are Biomarkers for Survival Prediction

Tapia, Pablo MD1; Gatica, Sebastian MSc2,3; Cortés-Rivera, Cristian MSc4; Otero, Carolina PhD4; Becerra, Alvaro PhD2,5; Riedel, Claudia A. PhD2,3; Cabello-Verrugio, Claudio PhD2,3,6; Kalergis, Alexis M. PhD3,7,8; Simon, Felipe PhD2,3

doi: 10.1097/CCM.0000000000003778
Clinical Investigations
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Objectives: To determine whether circulating endothelial cells from septic shock patients and from nonseptic shock patients are transformed in activated fibroblast by changing the expression level of endothelial and fibrotic proteins, whether the level of the protein expression change is associated with the amount of administered resuscitation fluid, and whether this circulating endothelial cell protein expression change is a biomarker to predict sepsis survival.

Design: Prospective study.

Setting: Medical-surgical ICUs in a tertiary care hospital.

Patients: Forty-three patients admitted in ICU and 22 healthy volunteers.

Interventions: None.

Measurements and Main Results: Circulating mature endothelial cells and circulating endothelial progenitor cells from septic shock and nonseptic shock patients showed evidence of endothelial fibrosis by changing the endothelial protein expression pattern. The endothelial proteins were downregulated, whereas fibroblast-specific markers were increased. The magnitude of the expression change in endothelial and fibrotic proteins was higher in the septic shock nonsurvivors patients but not in nonseptic shock. Interestingly, the decrease in the endothelial protein expression was correlated with the administered resuscitation fluid better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in the septic shock nonsurvivors patients but not in nonseptic shock. Notably, the significant difference between endothelial and fibrotic protein expression indicated a nonsurvival outcome in septic shock but not in nonseptic shock patients. Remarkably, area under the receiver operating characteristic curve analysis showed that endothelial protein expression levels predicted the survival outcome better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in septic shock but not in nonseptic shock patients.

Conclusions: Circulating endothelial cells from septic shock patients are acutely converted into fibroblasts. Endothelial and fibrotic protein expression level are associated with resuscitation fluid administration magnitude and can be used as biomarkers for an early survival diagnosis of sepsis.

1Unidad de Paciente Crítico Adulto, Hospital Clínico La Florida, La Florida, Santiago, Chile.

2Departamento de Ciencias Biologicas, Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile.

3Millennium Institute on Immunology and Immunotherapy, Santiago, Chile.

4Escuela de Química y Farmacia, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.

5Departamento de Ciencias Químicas y Biológicas, Facultad de Salud, Universidad Bernardo OHiggins, Santiago, Chile.

6Center for the Development of Nanoscience and Nanotechnology (CEDENNA), Universidad de Santiago de Chile, Santiago, Chile.

7Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

8Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

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Supported, in part, by research grants from Fondo Nacional de Desarrollo Científico y Tecnológico—Fondecyt 1161288, 21171566, and 1161646. Millennium Institute on Immunology and Immunotherapy P09-016-F. UNAB DI-741-15/N.

Drs. Gatica, Riedel, and Cabello-Verrugio received funding from Fondo Nacional de Desarrollo Científico y Tecnológico—Fondecyt. Dr. Kalergis received funding from Millennium Institute on Immunology and Immunotherapy. Dr. Simon’s institution received funding from Fondo Nacional de Desarrollo Científico y Tecnológico—Fondecyt, and he received support from Millennium Institute on Immunology and Immunotherapy P09-016-F. UNAB DI-741-15/N. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: fsimon@unab.cl

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