Modulation of endothelial glycocalyx structure under inflammatory conditions

Abstract

The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed.

Figure 1

Structure of glycocalyx: the backbone molecules, glycoproteins and proteoglycans; GAG chains linked to core proteins; soluble molecules derived from plasma or endothelium bound to proteoglycans; intertwined HA molecules; sheltered adhesive molecules.

Figure 2

Summary of methods which are currently used in direct or indirect visualization of glycocalyx in vivo and in vitro. Confocal laser scanning microscopy (CLSM), two-photon laser scanning microscopy (TPLSM), transmission electron microscopy (TEM), atomic force microscopy (AFM), intravital microscopy (IM), microparticle image velocimetry (μ-PIV), orthogonal polarization spectral imaging (OPS), and side-stream dark field imaging (SDF).

Figure 3

Overview of alternated glycocalyx functions as a result of its shedding which could lead to pathological states connected with various diseases. Matrix metalloproteinases (MMPs), reactive oxygen and nitrogen species (ROSs/RNSs), and tumor necrosis factor α (TNF-α).