title: Ventilator-induced lung injury increases expression of endothelial inflammatory mediators in the kidney.
abstract: In critical illness, such as sepsis or the acute respiratory distress syndrome, acute kidney injury (AKI) is common and associated with increased morbidity and mortality. Mechanical ventilation in critical illnesses is also a risk factor for AKI, but it is potentially modifiable. Injurious ventilation strategies may lead to the systemic release of inflammatory mediators from the lung due to ventilator induced lung injury (VILI). The systemic consequences of VILI are difficult to differentiate clinically from other systemic inflammatory syndromes, such as sepsis. The purpose of this study was to identify unique changes in the expression of inflammatory mediators in kidney tissue in response to VILI compared with systemic sepsis to gain insight into direct effects of VILI on the kidney. Four groups of mice were compared-mice with sepsis from cecal ligation and puncture (CLP), mice subjected to injurious mechanical ventilation with high tidal volumes (VILI), mice exposed to CLP followed by VILI (CLP+VILI), and sham controls. Protein expression of common inflammatory mediators in kidneys was analyzed using a proteome array and confirmed by Western blot analysis or ELISA. VEGF and VCAM-1 were found to be significantly elevated in kidneys from VILI mice compared with sham and CLP. Angiopoietin-2 was significantly increased in CLP+VILI compared with CLP alone and was also correlated with higher levels of AKI biomarker, neutrophil gelatinase-associated lipocalin. These results suggest that VILI alters the renal expression of VEGF, VCAM-1, and angiopoietin-2, and these proteins warrant further investigation as potential biomarkers and therapeutic targets.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, California.|Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Hepokoski
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Englert
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, Massachusetts; and.
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Baron
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, California.|Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Laura E
authors.identifier: 0000-0002-5091-2660
authors.initials: LE
authors.lastname: Crotty-Alexander
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, California.|Veterans Affairs San Diego Healthcare System, San Diego, California.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Fuster
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, California.
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Beitler
authors.affiliation: Division of Pulmonary and Critical Care Medicine, University of California San Diego, San Diego, California.
authors.forename: Atul
authors.initials: A
authors.lastname: Malhotra
authors.affiliation: Veterans Affairs San Diego Healthcare System, San Diego, California; p1singh@ucsd.edu.|Division of Nephrology and Hypertension, University of California San Diego, San Diego, California.
authors.forename: Prabhleen
authors.initials: P
authors.lastname: Singh
mesh_terms: D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008810:Mice, Inbred C57BL; D040901:Proteomics / Q000379:methods; D012121:Respiration, Artificial / Q000009:adverse effects*; D018805:Sepsis / Q000378:metabolism* / Q000382:microbiology; D015398:Signal Transduction; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000378:metabolism*
chemical_list: D042702:Angiopoietin-2; D015415:Biomarkers; D018836:Inflammation Mediators; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse
keywords: lung-kidney crosstalk