Endothelial cells (ECs) line all blood vessel walls and are exposed to the mechanical forces of blood flow which modulate their function and play a role in vascular regulation, remodelling and disease. The principal mechanical forces sensed by ECs are the shear stress of flowing blood on their apical surface, and the circumferential stress resisting blood pressure, which induces stretch in the cell body. 'Mechanotransduction' refers to the mechanisms by which these forces are transduced into biomolecular responses of the cells. Given the importance of endothelial mechanotransduction in cardiovascular physiology and pathology, numerous research efforts have been dedicated to identifying the mechanosensory component(s) of ECs. This review focuses on mechanotransduction of shear stress by ECs and considers the evidence in support of the surface glycocalyx acting as a mechanotransducer.

The surface of endothelial cells is decorated with a wide variety of membrane-bound macromolecules that constitute the glycocalyx. These include glycoproteins bearing acidic oligosaccharides with terminal sialic acids (SA), and proteoglycans with their associated glycosaminoglycan that include: heparan sulfate (HS), chondroitin sulfate (CS) and hyaluronic acid (HA). In this study enzymes were used to selectively degrade glycoclyx components from the surface of bovine aortic endothelial cells and the effects of these alterations on fluid shear-induced nitric oxide (NO) and prostacyclin (PGI 2 ) production were determined. Depletion of HS, HA and SA, but not CS, blocked shear-induced NO production. Surprisingly, the same enzyme depletions that blocked NO production had no influence on shear-induced PGI 2 production. The results may be interpreted in terms of a glypicancaveolae-eNOS mechanism for shear-induced NO transduction, with PGI 2 being transduced in basal adhesion plaques that sense the same reaction stress whether the glycocalyx is intact or not.

Garanich, Jeffrey S., Manolis Pahakis, and John M. Tarbell. Shear stress inhibits smooth muscle cell migration via nitric oxide-mediated downregulation of matrix metalloproteinase-2 activity.

Recent in vitro and in vivo studies have reported fluid shear stress-induced increases in endothelial layer hydraulic conductivity (L(p)) that are mediated by an increased production of nitric oxide (NO). Other recent studies have shown that NO induction by shear stress is mediated by the glycocalyx that decorates the surface of endothelial cells. Here we find that a selective depletion of the major components of the glycocalyx with enzymes can block the shear stress-induced response of L(p). Heparinase and hyaluronidase block shear-induced increases in L(p), which is consistent with their effects on NO production. But chondroitinase, which does not suppress shear-induced NO production, also inhibits shear-induced L(p). A further surprise is that treatment with the general proteolytic enzyme pronase does not suppress the shear L(p) response. We also find that heparinase does not alter baseline L(p) significantly, whereas chondroitinase, hyaluronidase, and pronase increase it significantly.

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