The Role of Glycocalyx and Caveolae in Vascular Homeostasis and Diseases

Abstract

This review highlights recent findings about the role that endothelial glycocalyx and caveolae play in vascular homeostasis. We describe the structure, synthesis, and function of glycocalyx and caveolae in vascular cells under physiological and pathophysiological conditions. Special focus will be given in glycocalyx and caveolae that are associated with impaired production of nitric oxide (NO) and generation of reactive oxygen species (ROS). Such alterations could contribute to the development of cardiovascular diseases, such as atherosclerosis, and hypertension.

Keywords: ROS; atherosclerosis; caveolae; eNOS; endothelial cells; glycocalyx; hypertension; vascular tone.

FIGURE 1

Schematic representation of caveola and glycocalyx proteins in endothelial cells (ECs) under non-pathological and pathological conditions. In non-pathological conditions, the glycocalyx proteins are intact and the coupled eNOS (dimeric form) is inactivated linked to Cav-1 protein. The eNOS is activated by shear stress mediated by Glypican-1 mechano-transduction as well as increase in calcium levels. The NO bioavailability can protect the cardiovascular system, and ROS produced by different sources stimulates the antioxidant system that also protects the cells of oxidative damage. In pathological conditions, the rise in ROS production mediated by pro-oxidant molecules as Ang II overtakes the antioxidant defenses. The ROS can degrade Cav-1, the eNOS is uncoupled (monomeric) that can be source of ROS, and NO bioavailability is reduced. ROS also stimulates the sheddases activity clivating the heparan sulfate from glypican and syndecan losing its ability to induce eNOS activation mediated by shear stress. Those frames with low NO levels can potentiate the cardiovascular risks.