The endothelial glycocalyx–placental extracellular vesicle axis in pre-eclampsia: A systematic review and translational framework from preconception vascular health to post-partum cardiovascular ageing

Pre-eclampsia is increasingly recognised as a systemic endothelial disorder initiated by placental stress and propagated through angiogenic, immune and extracellular vesicle (EV) signalling. Emerging data identify endothelial glycocalyx (EG) injury as a structural and functional bridge linking placental dysfunction to widespread maternal vascular damage and post-partum cardiovascular ageing. We conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020-guided systematic review spanning 2000–2025 across PubMed, Science Direct, Taylor and Francis and AHA Journals to synthesise evidence on the EG–EV axis in pre-eclampsia. A total of 1268 records were retrieved; after exclusion, 35 studies met the inclusion criteria, with 20 rated low-to-moderate risk of bias forming the mechanistic core for synthesis. Across study designs, placental hypoxia triggered the release of syncytiotrophoblast-derived EVs enriched with anti-angiogenic and proteolytic cargos (miRNAs, neprilysin and sFlt-1), which impaired endothelial function and promoted glycocalyx shedding, as reflected by elevated syndecan-1 and heparan sulphate levels and thickening of the perfused boundary region. Although methodological heterogeneity across EV isolation and EG quantification platforms contributed to variable effect magnitudes, directional concordance supported a unified mechanistic model linking angiogenic imbalance, endothelial degradation and vascular dysfunction. These pathways delineate a continuum from placental signalling to lifelong vascular vulnerability. Translationally, composite biomarker panels integrating EV, cfRNA and EG markers show promise for early detection and post-partum cardiovascular risk stratification. This synthesis reframes pre-eclampsia as a vascular communication disorder and identifies actionable opportunities for biomarker-driven prediction, endothelial protection and preventive cardiovascular care.