Endothelial-erythrocyte glycocalyx exchange enables liquid biopsies of endothelial function
The luminal surface of blood vessels is covered by a hydrated mesh of sugars and proteins termed the endothelial glycocalyx. The glycocalyx forms a permeability barrier and helps regulate leucocyte migration. Directly detecting glycocalyx damage could provide a major advance in vascular health monitoring. Here we show that red blood cell glycocalyx mirrors the endothelial glycocalyx in health and disease. Using peripherally sampled blood, we confirm that red blood cell glycocalyx measurements predict cardiac and renal endothelial glycocalyx alterations and direct measures of endothelial barrier function in male rats. To investigate the underlying mechanism, we use Azide-Alkyne cycloaddition ('Click' chemistry) to confirm that contact between endothelial and red blood cells results in continual reciprocal transfer of glycocalyx components. These discoveries facilitate real-time monitoring of endothelial damage in patients whilst simultaneously providing a potential explanation as to how red blood cells maintain their glycocalyx during circulation.
Authors
- B. Foster
- Gavin I. Welsh (ORCID: https://orcid.org/0000-0002-2148-6658)
- Judit Sutak (ORCID: https://orcid.org/0000-0002-6189-906X)
- Matthew Butler (ORCID: https://orcid.org/0000-0002-9814-8008)
- Michael Crompton (ORCID: https://orcid.org/0000-0001-6463-9020)
- Simon C. Satchell (ORCID: https://orcid.org/0000-0001-5276-4537)
- Monica Gamez (ORCID: https://orcid.org/0000-0002-6558-2123)
- Yamaguchi Yu
- Jasmine Aldam
- Laura Carey
- Charley Heffer
- Raina R. Ramnath (ORCID: https://orcid.org/0000-0001-8472-5081)
- Jialu Li
- Yan Qiu
- Colin Down
- Chris Neal
- Victoria Bills
- Stephen Cross (ORCID: https://orcid.org/0000-0003-3565-0479)
- Laura Skinner
Institutions
- North Bristol NHS Trust (GB)
- University of the West of England (GB)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Discovery Institute (US)
- University Hospitals Bristol NHS Foundation Trust (GB)
- University of Bristol (GB)
- Bristol Robotics Laboratory (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-05-12
- DOI
- https://doi.org/10.1038/s41467-026-71848-4
- Primary Topic
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Foundation for the National Institutes of Health
- British Heart Foundation
- Kidney Research UK
- Diabetes UK
- National Institutes of Health
- Elizabeth Blackwell Institute for Health Research, University of Bristol
- Medical Research Council