Endothelial Glycocalyx Degradation as a Central Mechanism in Premature Atherosclerotic Cardiovascular Disease

Premature atherosclerotic cardiovascular disease (ASCVD) poses a substantial clinical burden. Endothelial glycocalyx injury has been proposed as a contributor to vascular dysfunction and atherosclerotic processes, but its role in premature ASCVD remains uncertain. This narrative review examines evidence on glycocalyx structure and degradation, associated vascular mechanisms, candidate biomarkers, and potential therapeutic approaches. Literature published from 2010 to March 2026 was identified through PubMed, Scopus, Web of Science, and Google Scholar using terms related to the endothelial glycocalyx, atherosclerosis, endothelial dysfunction, and cardiovascular disease. Earlier foundational studies were also considered. Experimental and clinical literature links glycocalyx injury with altered vascular permeability, mechanotransduction, nitric oxide signaling, and inflammatory cell interactions. Oxidative stress, hyperglycemia, inflammation, and disturbed flow have been investigated as potential contributors to glycocalyx damage. Circulating glycocalyx components, including syndecan-1, are being studied as markers of endothelial injury, but their value for predicting premature ASCVD has not been established. Although glycocalyx preservation and restoration are potential therapeutic research directions, evidence that these approaches prevent premature cardiovascular events is lacking. Overall, glycocalyx injury is a biologically plausible contributor to atherosclerotic processes; prospective human studies are needed to establish its causal and predictive roles in premature ASCVD.