Noninvasive sublingual microvascular imaging reveals sex‐specific reduction in glycocalyx barrier properties in patients with coronary artery disease

Abstract

Background: Risk factors for coronary artery disease (CAD) have been associated with endothelial dysfunction and degradation of the endothelial glycocalyx. This study was designed to compare sublingual microvascular perfusion and glycocalyx barrier properties in CAD patients and controls using noninvasive side stream darkfield imaging. Methods: Imaging of the sublingual microvasculature was performed in 52 case subjects (CAD confirmed by left heart catheterization) and 63 controls (low Framingham risk score). Red blood cell (RBC) filling percentage and functional microvascular density, measures of microvascular perfusion, and perfused boundary region (PBR), an index of glycocalyx barrier function, were measured in microvessels with a diameter ranging from 5-25 µm. Results: RBC filling percentage was lower in patients with CAD compared to controls (p < .001). Functional microvascular density did not differ between groups.The overall PBR was marginally greater in the CAD group compared to the control group (p = .08). PBR did not differ between male CAD cases and controls (p = .17).However, PBR was greater in females with CAD compared with female controls (p = .04), indicating reduced glycocalyx barrier function. This difference became more pronounced after adjusting for potential confounders. Conclusions: Our data suggest that patients with CAD are characterized by a reduction in percentage of time microvessels are occupied by RBCs. In addition, CAD is significantly associated with impaired sublingual microvascular glycocalyx barrier function in women but not men. More research is needed to determine the significance of peripheral microvascular dysfunction in the pathophysiology of CAD, and how this may differ by sex. K E Y W O R D Scoronary artery disease, endothelial glycocalyx, imaging, microvascular dysfunction, sex differences

Human glycocalyx shedding: Systematic review and critical appraisal

“…In chronic diseases, compensatory responses may offset changes in shedding or expression. For example, in one study assessment of the glycocalyx by SDF imaging showed no significant difference in glycocalyx dimensions between patients with and without cardiovascular disease 227 . However, two studies have reported elevations in sdc‐1 and HA in patients with cardiovascular disease 159,184 .…”

“…For example, in one study assessment of the glycocalyx by SDF imaging showed no significant difference in glycocalyx dimensions between patients with and without cardiovascular disease. 227 However, two studies have reported elevations in sdc-1 and HA in patients with cardiovascular disease. 159,184 Support for compensatory reaction(s) can be inferred from an in vivo study of the glycocalyx in sdc-1 knock-out (KO) mice where Savery et al used micro-particle velocimetry to determine the presence of a hydrodynamically significant cell surface layer.…”

Sex‐related associations of high‐density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients

“…In coronary artery disease, both males and females have significantly impaired sublingual microvascular perfusion compared to controls. However, women, but not men, exhibited a significantly larger PBR, indicting a reduction in glycocalyx barrier function suggesting sex dependency 32 …”

Investigation of Wall Shear Stress in Cardiovascular Research and in Clinical Practice—From Bench to Bedside

“…Thus, eGCX thickness inversely correlates with microvascular perfusion of this boundary region [ 100 ]. Increased PBR values were described in patients with CAD and cerebral atherosclerosis, indicating an impaired eGCX during atherosclerosis progression [ 101 , 102 ].…”