ROLE OF ENDOTHELIAL GLYCOCALYX DISRUPTION IN ATHEROSCLEROSIS PROGRESSION

Abstract

Endothelial glycocalyx disruption is increasingly recognized as a critical event in the pathogenesis of atherosclerosis. This study aimed to investigate the clinical, biochemical, and cellular implications of glycocalyx degradation in patients with established atherosclerotic cardiovascular disease. A total of 120 patients were evaluated through plasma biomarker profiling, sublingual microvascular imaging, and carotid and coronary imaging. Glycocalyx degradation was confirmed by elevated levels of syndecan-1 (68.5 ± 15.2 ng/mL), hyaluronic acid (137.9 ± 29.4 ng/mL), and heparan sulfate (102.3 ± 23.1 ng/mL). Both biochemical abnormalities and structural changes were strongly associated with disease severity, as seen by a relationship between coronary segment disease and the measured number of damaged coronary arteries (r = 0.58, p < 0.001) and between higher carotid intima-media thickness and the presence of atherosclerosis (r = 0.61, p < 0.001).  Endothelial damage was shown by elevated oxidative stress and inflammatory markers as well as lowered nitric oxide production and increased expression of adhesion molecules such as VCAM-1, ICAM-1 and E-selectin.  Increased perfused border region (PBR: Indicator of lost glycocalyx was confirmed by measurements of increased perfused border zone area, decreased capillary density and reduced red blood cell encirclement as seen on non-invasive imaging.  ECs incubated with oxLDL, TNF-α and high glucose in cell culture revealed enhanced ROS production (by 2.8-fold), reduced nitric oxide synthesis and increased glycocalyx shedding (up to 181%).  The findings show that glycocalyx degradation likely plays a crucial role in the link between endothelial dysfunction, oxidative stress and inflammation to progression of atherosclerotic plaque.  The research highlights the clinical benefit of glycocalyx-protective treatments for preventing or repairing artery damage in atherosclerosis and underscores the importance of glycocalyx measurements as tools for early intervention.