The role of the endothelial glycocalyx in advanced age and cardiovascular disease

Abstract

The endothelial glycocalyx is a gel-like structure that is bound to the luminal surface of the vascular endothelium. At the interface between flowing blood and endothelial cells, the glycocalyx has several functions that are critical for the maintenance of a healthy vasculature, particularly in regard to the vascular endothelium. Within the vasculature, the glycocalyx modulates vascular resistance to maintain blood flow homogeneity in the microcirculation, mechanotransduces fluid shear stress to the endothelium, and buffers endothelial cells from plasma oxidants, cytokines, and circulating immune cells. In advanced age and cardiovascular disease (CVD), the glycocalyx is deteriorated. Moreover, glycocalyx deterioration may precede traditional measurements of age-related vascular dysfunction, such as impaired endothelium-dependent dilation and large artery stiffness, suggesting that a deteriorated glycocalyx could initiate age-related CVD pathology.

Figure 1.

Working hypothesis demonstrating how the deterioration of the glycocalyx in advanced age leads to age-related cardiovascular disease.

Figure 2.

Electron micrograph of a mouse soleus microvessel with a glycocalyx that lines its endothelial wall. EC, endothelial cell; RBC, red blood cell.

Figure 3.

The role of glycocalyx in maintaining the blood flow distribution. Figure 3A depicts the arterial vasculature in youth, where the glycocalyx contributes to the maintenance of blood flow homogeneity, protects endothelial cells from the inflammatory cytokines, oxidants, and immune cells, and mechanotransduces shear stress to the endothelial cells stimulating nitric oxide (NO) production by endothelial NO synthase (eNOS). Figure 3B depicts the arterial vasculature in advanced age. Age-related glycocalyx deterioration results in greater blood flow heterogeneity between branch points, while impairing mechanotransduction of shear stress to the endothelium lessening NO production, and leaving the endothelium vulnerable to plasma inflammatory cytokines, oxidants, and immune cell adhesion that further reduce NO bioavailability.