ENDOTHELIAL GLYCOCALYX DYSFUNCTION IN ATHEROSCLEROSIS: AN OVERLOOKED MECHANISM

Abstract

The Endothelial glycocalyx represents a dynamic, gel-like structure lining the luminal surface of vascular endothelial cells, playing a crucial role in maintaining vascular homeostasis. Traditionally, atherosclerosis has been primarily attributed to lipid accumulation and inflammation; however, emerging evidence highlights glycocalyx dysfunction as a critical early event in disease initiation and progression. This review aims to explore the structural and functional properties of the endothelial glycocalyx and its role in the pathogenesis of atherosclerosis. Disruption of the glycocalyx increases endothelial permeability, facilitates low-density lipoprotein (LDL) infiltration, and enhances leukocyte adhesion. Furthermore, glycocalyx degradation impairs mechanotransduction of shear stress, leading to endothelial dysfunction and pro-inflammatory signaling. Multiple factors, including oxidative stress, hyperglycemia, dyslipidemia, and inflammatory mediators, contribute to glycocalyx shedding. The loss of this protective barrier not only accelerates plaque formation but also contributes to plaque instability. Recent advances in imaging and biomarker research have improved the ability to assess glycocalyx integrity in vivo. Therapeutic strategies targeting glycocalyx preservation and restoration, including lifestyle modification and pharmacological interventions, are emerging as promising approaches in cardiovascular prevention.

In conclusion, endothelial glycocalyx dysfunction represents an underrecognized but fundamental mechanism in atherosclerosis. Integrating this concept into current pathophysiological models may enhance early diagnosis and open new avenues for targeted therapy.