Sepsis therapies aim to protect the endothelial glycocalyx, review finds

A systematic review published in Molecular Biology Reports concludes that the endothelial glycocalyx, a delicate carbohydrate-rich layer lining the inside of blood vessels, is a promising but still unproven therapeutic target in sepsis. The review, authored by Nagwa I. Helal, Tarek M. Mostafa, Kareem A. El-meslmany and Rehab H. Werida, was published on 23 October 2026 as volume 53, article number 1796 of the journal.

The endothelial glycocalyx, abbreviated eGCX, degrades prominently during sepsis. According to the review, this degradation contributes to endothelial dysfunction, increased vascular permeability, inflammation, microvascular thrombosis and organ failure. Despite its recognized importance, therapies aimed specifically at the glycocalyx are not currently part of standard sepsis management, which motivated the authors to map the existing evidence base.

The researchers searched PubMed, Scopus, Web of Science, the Cochrane Library and Google Scholar through August 2026. Eligible studies were human or animal investigations of eGCX-directed interventions in sepsis or experimental sepsis models. Outcomes of interest included circulating biomarkers such as syndecan-1, heparan sulfate and hyaluronan, microcirculatory measures including the perfused boundary region, and structural assessment of the glycocalyx by microscopy. Risk of bias was evaluated with the RoB 2, SYRCLE and ROBINS-I tools.

Twenty-one studies met the inclusion criteria: 17 animal studies and only 4 human studies. This imbalance is the review’s central caveat. Most of what is known about protecting the glycocalyx in sepsis comes from experimental models rather than from clinical trials in patients, and the authors state explicitly that well-designed clinical studies using standardized eGCX outcomes are needed.

The interventions covered a strikingly diverse range. They included ascorbic acid, sulodexide, doxycycline, activated protein C, heparin-based therapies, plasma-derived and recombinant antithrombin, recombinant thrombomodulin, therapeutic plasma exchange, colivelin, liposomal nanocarriers carrying preassembled glycocalyx material, and rhamnan sulfate. Several of these reduced glycocalyx shedding, meaning less of the protective layer was sloughed into the circulation, and improved endothelial barrier or microvascular function.

In some experimental models, the interventions went further: they preserved or restored the glycocalyx ultrastructure, the fine architecture of the layer itself, as seen under microscopic assessment. The review’s significance statement summarizes the conclusion plainly: glycocalyx preservation can be a target of interest in sepsis using several promising interventions.

The measured biomarkers reflect different aspects of glycocalyx damage. Together these endpoints give researchers ways to quantify whether an intervention is actually protecting the endothelial surface.

The review’s overall message is cautiously optimistic. The endothelial glycocalyx represents a promising therapeutic target in sepsis, the authors conclude, but the evidence remains predominantly preclinical. Translating these findings into standard sepsis care will require rigorous human trials with consistent, standardized ways of measuring glycocalyx integrity, since the four human studies identified to date are far too limited to support treatment recommendations.

Subject of Research: Therapeutic strategies for preserving endothelial glycocalyx integrity in sepsis

Article Title: Promising therapeutic interventions for preserving endothelial glycocalyx integrity in sepsis: a systematic review

Article References: Helal, N. I., Mostafa, T. M., El-meslmany, K. A., & Werida, R. H. (2026). Promising therapeutic interventions for preserving endothelial glycocalyx integrity in sepsis: a systematic review. Molecular Biology Reports, 53(1), Article 1796. https://doi.org/10.1007/s11033-026-12889-2

Image Credits: AI Generated

DOI: 10.1007/s11033-026-12889-2

Keywords: sepsis, endothelial glycocalyx, systematic review, syndecan-1, vascular permeability, microcirculation, ascorbic acid, sulodexide, therapeutic plasma exchange, preclinical evidence, Promising, therapeutic