The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

Authors
Schmidt, E.P.
Li, G.
Li, L.
Fu, L.
Yang, Y.
Overdier, K.H.
Douglas, I.S.
Linhardt, Robert J.
ORCID
https://orcid.org/0000-0003-2219-5833
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Issue Date
2014
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Terms of Use
Attribution 3.0 United States
CC BY : this license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. Credit must be given to the authors and the original work must be properly cited.
Full Citation
The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults, E. P. Schmidt, G. Li, L. Li, L. Fu, Y. Yang, K. H. Overdier, I. S. Douglas, R. J. Linhardt, Journal of Biological Chemistry, 289, 8194–8202, 2014.
Abstract
Systemic inflammatory illnesses (such as sepsis) are marked by degradation of the endothelial glycocalyx, a layer of glycosaminoglycans (including heparan sulfate, chondroitin sulfate, and hyaluronic acid) lining the vascular lumen. We hypothesized that different pathophysiologic insults would produce characteristic patterns of released glycocalyx fragments. We collected plasma from healthy donors as well as from subjects with respiratory failure due to altered mental status (intoxication, ischemic brain injury), indirect lung injury (non-pulmonary sepsis, pancreatitis), or direct lung injury (aspiration, pneumonia). Mass spectrometry was employed to determine the quantity and sulfation patterns of circulating glycosaminoglycans. We found that circulating heparan sulfate fragments were significantly (23-fold) elevated in patients with indirect lung injury, while circulating hyaluronic acid concentrations were elevated (32-fold) in patients with direct lung injury. N-Sulfation and tri-sulfation of heparan disaccharides were significantly increased in patients with indirect lung injury. Chondroitin disaccharide sulfation was suppressed in all groups with respiratory failure. Plasma heparan sulfate concentrations directly correlated with intensive care unit length of stay. Serial plasma measurements performed in select patients revealed that circulating highly sulfated heparan fragments persisted for greater than 3 days after the onset of respiratory failure. Our findings demonstrate that circulating glycosaminoglycans are elevated in patterns characteristic of the etiology of respiratory failure and may serve as diagnostic and/or prognostic biomarkers of critical illness.
Description
Journal of Biological Chemistry, 289, 8194–8202
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Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
The American Society for Biochemistry and Molecular Biology (ASBMB) and Elsevier
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
https://harc.rpi.edu/
Access
A full text version is available in DSpace@RPI
CC BY — Creative Commons Attribution