Does diabetes modify the effect of heparin on plasma proteins? - A proteomic search for plasma protein biomarkers for diabetes-related endothelial dysfunction

Mette Soerensen*, Birgit Debrabant, Ulrich Halekoh, Jacob Eifer Møller, Christian Hassager, Martin Frydland, Jacob Hjelmborg, Hans Christian Beck, Lars Melholt Rasmussen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Aim: Heparin administration affects the concentrations of many plasma proteins through their displacement from the endothelial glycocalyx. A differentiated protein response in diabetes will therefore, at least partly, reflect glycocalyx changes. This study aims at identifying biomarkers of endothelial dysfunction in diabetes by statistical exploration of plasma proteome data for interactions between diabetes status and heparin treatment. Methods: Diabetes-by-heparin interactions in relation to protein levels were inspected by regression modelling in plasma proteome data from 497 patients admitted for acute angiography. Analyses were conducted separately for all 273 proteins and as set-based analyses of 44 heparin-relevant proteins identified by gene ontology analysis and 42 heparin-influenced proteins previously reported. Results: Seventy-five patients had diabetes and 361 received heparin before hospitalization. The proteome-wide analysis displayed no proteins with diabetes-heparin interaction to pass correction for multiple testing. The overall set-based analyses revealed significant association for both protein sets (p-values<2*10 −4), while constraining on opposite directions of effect in diabetics and none-diabetics was insignificant (p-values = 0.11 and 0.17). Conclusions: Our plasma proteome-wide interaction approach supports that diabetes influences heparin effects on protein levels, however the direction of effects and individual proteins could not be definitively pinpointed, likely reflecting a complex protein-basis for glycocalyx dysfunction in diabetes.

Original languageEnglish
Article number107906
JournalJournal of Diabetes and Its Complications
Volume35
Issue number6
ISSN1056-8727
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Diabetes
  • Endothelial dysfunction
  • Heparin
  • Interaction models
  • Mediation
  • Proteome data

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