Targeting the endothelial glycocalyx to reduce cardiovascular disease
Creators: name: Gimblet, Colin J.
Publisher: name: University of Iowa
Year: 2026

description: Cardiovascular disease is the leading cause of death worldwide, in part, because of age-related vascular endothelial dysfunction. One potential cause of vascular endothelial dysfunction with advancing age is degradation of the endothelial glycocalyx. The endothelial glycocalyx is a dynamic, gel-like structure of glycoproteins, proteoglycans, and glycosaminoglycans that lines the luminal surface of the vascular endothelium and serves as the interface between circulating blood and the vascular wall. Additionally, preclinical research suggests that removal of the endothelial glycocalyx impairs vascular endothelial function and that restoring the endothelial glycocalyx improves vascular endothelial function. However, this idea has yet to be tested in humans. Thus, we attempted to address these critical gaps by completing the two following two aims: Aim 1) determine whether acute heparin administration degrades the endothelial glycocalyx and reduces vascular endothelial function in healthy young adults, and Aim 2) determine whether glycocalyx-target therapy increases endothelial glycocalyx thickness and vascular endothelial function in older adults.
description: In aim 1, healthy younger adults (n=19, aged 18-39 years, 53% female) underwent measurements of the endothelial glycocalyx and vascular endothelial function at baseline and after a single intravenous bolus 5000 U dose of heparin. Following acute heparin administration, there was no change in endothelial glycocalyx thickness or circulating glycocalyx components. Additionally, there was no difference in vascular endothelial function assessed via brachial artery flow-mediated dilation or plasma nitrite after heparin treatment. Our pilot study suggests that a single intravenous bolus dose of heparin does not result in acute endothelial glycocalyx degradation or vascular endothelial dysfunction in healthy younger adults.
description: In aim 2, we enrolled older men and postmenopausal women (n=23, aged 60-83 years, 52% female) in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-week Endocalyx Pro supplementation (3,712 mg/day) on endothelial glycocalyx thickness and vascular endothelial function. Compared with placebo, Endocalyx Pro did not significantly improve vascular endothelial function determined by flow-mediated dilation. Additionally, Endocalyx pro did not improve endothelial glycocalyx thickness significantly greater than placebo. However, compared with placebo, Endocalyx Pro did significantly improve flow-mediated dilation normalized to the shear stress stimulus and increase endothelial glycocalyx thickness in a select microvessel region. Overall, our pilot study suggests that Endocalyx Pro may be a promising therapy to improve endothelial glycocalyx thickness and vascular endothelial function in older adults. Larger clinical trials are needed to expand upon our pilot findings.
description: Taken together, this dissertation extended our knowledge on the endothelial glycocalyx’s relation with vascular endothelial function in humans. Future researchers should test alternative methods to assess the effect of experimental endothelial glycocalyx degradation on vascular endothelial function in humans. Additionally, larger clinical trials are needed to determine whether glycocalyx-targeted therapy is a viable treatment option to restore endothelial glycocalyx thickness and vascular endothelial function with aging and other chronic diseases in humans.