ENDOTHELIAL GLYCOCALYX AND ATHEROSCLEROSIS: FROM MOLECULAR MECHANISMS TO THERAPEUTIC OPPORTUNITIES

Abstract

The endothelial glycocalyx is a highly dynamic, carbohydrate-rich layer that lines the luminal surface of blood vessels and plays a fundamental role in vascular homeostasis. Although once considered a passive structural barrier, it is now recognized as a critical regulator of endothelial permeability, mechanotransduction, leukocyte adhesion, and thrombosis. Its degradation has been implicated as a pivotal event in the initiation and progression of atherosclerosis. This review synthesizes current evidence on the structure, physiological functions, mechanisms of degradation, and clinical significance of the endothelial glycocalyx in the context of atherosclerosis. We also highlight diagnostic approaches and emerging therapeutic strategies aimed at glycocalyx preservation and restoration. A growing body of evidence demonstrates that glycocalyx degradation precedes overt endothelial dysfunction and facilitates lipid infiltration, immune cell recruitment, and thrombogenic transformation of the vascular surface. Multiple triggers, including pro-inflammatory cytokines, oxidative stress, disturbed shear stress, and metabolic derangements, contribute to the loss of glycocalyx integrity. Clinical studies have identified circulating glycocalyx fragments as biomarkers of vascular damage and cardiovascular risk. Experimental and early clinical data suggest that interventions such as glycosaminoglycan supplementation, enzyme inhibition, antioxidant therapy, and lifestyle modification can restore glycocalyx structure and function. Preservation of the endothelial glycocalyx represents a promising therapeutic frontier in the prevention and treatment of atherosclerosis. Continued advances in glycocalyx imaging, molecular profiling, and targeted interventions are expected to redefine vascular risk stratification and foster the development of glycocalyx-centered therapies.