---
title: "Therapies Targeting the Endothelial Glycocalyx in Sepsis: Systematic Review Findings"
id: "pubmed-42909518"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42909518"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42909518/"
doi: "10.1007/s11033-026-12889-2"
published_at: "2026-10-23T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Therapies Targeting the Endothelial Glycocalyx in Sepsis: Systematic Review Findings
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42909518
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42909518/)
- **DOI:** [10.1007/s11033-026-12889-2](https://doi.org/10.1007%2Fs11033-026-12889-2)
- **Published At:** 2026-10-23T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The systematic review searched PubMed, Scopus, Web of Science, Cochrane Library and Google Scholar through August 2026 and included 21 studies addressing **endothelial glycocalyx** (eGCX) interventions in sepsis. - Twenty-one studies met inclusion: 17 were preclinical (animal) investigations and 4 were human studies; investigators reported a predominance of experimental models over clinical trials. - Outcomes assessed included circulating biomarkers (notably **syndecan-1**, heparan sulfate, hyaluronan), microcirculatory indices such as perfused boundary region, and structural evaluation by microscopy. - The review evaluated risk of bias using RoB 2 for randomized trials, SYRCLE for animal studies, and ROBINS-I for non-randomized studies; the source reported that risk-of-bias assessment was performed but did not list tool-specific scores in the abstract. - Interventions studied encompassed ascorbic acid, sulodexide, doxycycline, activated protein C, heparin-based therapies, antithrombin, recombinant thrombomodulin, therapeutic plasma exchange, colivelin, liposomal nanocarriers of preassembled eGCX, and rhamnan sulfate. - Across several experimental models, some interventions reduced eGCX shedding, improved endothelial barrier or microvascular function, and in certain cases preserved or restored eGCX ultrastructure as observed by microscopy. - The review team noted that most evidence remains preclinical; human data were limited to four studies and the abstract did not provide specific clinical outcomes or numeric effect sizes. - The authors concluded that the **eGCX** is a viable therapeutic target in sepsis but emphasized the need for well-designed clinical studies using standardized eGCX outcome measures before clinical adoption.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt. * 2 Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt. * 3 Department of Critical care Medicine, Damanhour Medical National Institute, General Organization for Teaching Hospitals and Institutes, Damanhour, Egypt. * 4 Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt. rehabwrieda@pharm.dmu.edu.eg. * 5 Department of Clinical Pharmacy, Faculty of Pharmacy, AlSalam University, Tanta, Gharbia, 31511, AL Gharbia, Egypt. rehabwrieda@pharm.dmu.edu.eg. * PMID: **42909518** * DOI: [ 10.1007/s11033-026-12889-2 ](https://doi.org/10.1007/s11033-026-12889-2) Item in Clipboard Review # Promising therapeutic interventions for preserving endothelial glycocalyx integrity in sepsis: a systematic review Nagwa I Helal et al. Mol Biol Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Mol Biol Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Mol+Biol+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Mol+Biol+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) . 2026 Oct 23;53(1):1796. doi: 10.1007/s11033-026-12889-2. ### Authors [Nagwa I Helal](https://pubmed.ncbi.nlm.nih.gov/?term=Helal+NI&cauthor_id=42909518)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42909518/#short-view-affiliation-1 "Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt."), [Tarek M Mostafa](https://pubmed.ncbi.nlm.nih.gov/?term=Mostafa+TM&cauthor_id=42909518)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42909518/#short-view-affiliation-2 "Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt."), [Kareem A El-Meslmany](https://pubmed.ncbi.nlm.nih.gov/?term=El-Meslmany+KA&cauthor_id=42909518)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42909518/#short-view-affiliation-3 "Department of Critical care Medicine, Damanhour Medical National Institute, General Organization for Teaching Hospitals and Institutes, Damanhour, Egypt."), [Rehab H Werida](https://pubmed.ncbi.nlm.nih.gov/?term=Werida+RH&cauthor_id=42909518)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42909518/#short-view-affiliation-4 "Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt. rehabwrieda@pharm.dmu.edu.eg.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42909518/#short-view-affiliation-5 "Department of Clinical Pharmacy, Faculty of Pharmacy, AlSalam University, Tanta, Gharbia, 31511, AL Gharbia, Egypt. rehabwrieda@pharm.dmu.edu.eg.") ### Affiliations * 1 Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt. * 2 Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt. * 3 Department of Critical care Medicine, Damanhour Medical National Institute, General Organization for Teaching Hospitals and Institutes, Damanhour, Egypt. * 4 Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, Damanhour University, Damanhour, 22514, Egypt. rehabwrieda@pharm.dmu.edu.eg. * 5 Department of Clinical Pharmacy, Faculty of Pharmacy, AlSalam University, Tanta, Gharbia, 31511, AL Gharbia, Egypt. rehabwrieda@pharm.dmu.edu.eg. * PMID: **42909518** * DOI: [ 10.1007/s11033-026-12889-2 ](https://doi.org/10.1007/s11033-026-12889-2) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Endothelial Glycocalyx (eGCX) degradation is a major pathophysiological event in sepsis, contributing to endothelial dysfunction, vascular permeability, inflammation, microvascular thrombosis, and organ failure. Despite its importance, eGCX-targeted therapies are not currently incorporated into standard sepsis management. This systematic review summarized clinical and preclinical evidence on therapeutic and experimental strategies aimed at preserving or restoring eGCX integrity in sepsis. PubMed, Scopus, Web of Science, the Cochrane Library, and Google Scholar were searched through August 2026. Eligible human and animal studies evaluated eGCX-directed interventions in sepsis or experimental sepsis models. Outcomes included circulating biomarkers such as syndecan-1, heparan sulfate, and hyaluronan, microcirculatory measures including perfused boundary region, and structural assessment by microscopy. Risk of bias was assessed using RoB 2, SYRCLE, and ROBINS-I. Twenty-one studies were included, comprising 17 animal and 4 human studies. Interventions included ascorbic acid, sulodexide, doxycycline, activated protein C, heparin-based therapies, antithrombin, recombinant thrombomodulin, therapeutic plasma exchange, colivelin, liposomal nanocarriers of preassembled eGCX, and rhamnan sulfate. Several interventions reduced eGCX shedding, improved endothelial barrier or microvascular function, and, in some experimental models, preserved or restored eGCX ultrastructure. Overall, the eGCX represents a promising therapeutic target in sepsis; however, most evidence remains preclinical, and well-designed clinical studies using standardized eGCX outcomes are needed. **Keywords:** Perfused boundary region; Sepsis; Syndecan-1; eGCX; eGCX shedding; eGCX-targeted interventions. © 2026. The Author(s), under exclusive licence to Springer Nature B.V. [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Consent for publication: Not applicable. Conflict of interest: The authors declare no conflict of interest. Consent to participate: Not applicable. Ethical Approval/ Protocol Registration: Ethical approval was not required for this study as it is a systematic review based on previously published data. The study protocol was registered in the PROSPERO database (Registration No. CRD420251270767). Trial Registration: PROSPERO registration number CRD420251270767. Competing interests: The authors declare no competing interests. ## References 1. 1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al (2016) The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA 315(8):801–810. - [DOI](https://doi.org/10.1001/jama.2016.0287) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26903338/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4968574/) 2. 1. GBD 2021 Global Sepsis Collaborators (2025) Global, regional, and national sepsis incidence and mortality, 1990–2021: a systematic analysis. Lancet Glob Health 13(12):e2013–e2026. - [DOI](https://doi.org/10.1016/s2214-109x\(25\)00356-0) 3. 1. La Via L, Sangiorgio G, Stefani S, Marino A, Nunnari G, Cocuzza S et al (2024) The Global Burden of Sepsis and Septic Shock. Epidemiol Basel Switz 5(3):456–478. - [DOI](https://doi.org/10.3390/epidemiologia5030032) 4. 1. Martín-Fernández M, Tamayo-Velasco Á, Aller R, Gonzalo-Benito H, Martínez-Paz P, Tamayo E (2021) Endothelial Dysfunction and Neutrophil Degranulation as Central Events in Sepsis Physiopathology. Int J Mol Sci 22(12):6272. - [DOI](https://doi.org/10.3390/ijms22126272) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34200950/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8230689/) 5. 1. Hu Z, Cano I, D’Amore PA (2021) Update on the Role of the Endothelial Glycocalyx in Angiogenesis and Vascular Inflammation. Front Cell Dev Biol 9:734276. - [DOI](https://doi.org/10.3389/fcell.2021.734276) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34532323/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/8438194/) Show all 68 references ## Publication types * Systematic Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Systematic+Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Systematic+Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Review Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Review%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Review) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) ## MeSH terms * Animals Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Animals%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Animals) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Ascorbic Acid / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Ascorbic+Acid%2Fpharmacology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Ascorbic+Acid) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Ascorbic Acid / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Ascorbic+Acid%2Ftherapeutic+use%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Ascorbic+Acid) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Biomarkers / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Biomarkers%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Biomarkers) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Doxycycline / pharmacology Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Doxycycline%2Fpharmacology%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Doxycycline) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Doxycycline / therapeutic use Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Doxycycline%2Ftherapeutic+use%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Doxycycline) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Endothelium, Vascular* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Endothelium%2C+Vascular%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Endothelium%2C+Vascular) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Glycocalyx* / drug effects Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glycocalyx%2Fdrug+effects%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glycocalyx) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Glycocalyx* / metabolism Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glycocalyx%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glycocalyx) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42909518/) * Glycosaminoglycans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glycosaminoglycans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glycosaminoglycans) * [ Add to Search ](http
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