Mechanosensing at the Vascular Interface

Abstract

Mammals are endowed with a complex set of mechanisms that sense mechanical forces imparted by blood flow to endothelial cells (ECs), smooth muscle cells, and circulating blood cells to elicit biochemical responses through a process referred to as mechanotransduction. These biochemical responses are critical for a host of other responses, including regulation of blood pressure, control of vascular permeability for maintaining adequate perfusion of tissues, and control of leukocyte recruitment during immunosurveillance and inflammation. This review focuses on the role of the endothelial surface proteoglycan/glycoprotein layer—the glycocalyx (GCX)—that lines all blood vessel walls and is an agent in mechanotransduction and the modulation of blood cell interactions with the EC surface. We first discuss the biochemical composition and ultrastructure of the GCX, highlighting recent developments that reveal gaps in our understanding of the relationship between composition and spatial organization. We then consider the roles of the GCX in mechanotransduction and in vascular permeability control and review the prominent interaction of plasma borne sphingosine-1 phosphate (S1P), which has been shown to regulate both the composition of the GCX and the endothelial junctions. Finally, we consider the association of GCX degradation with inflammation and vascular disease and end with a final section on future research directions.

Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release

“…The ability of endothelial cells to respond to fluid shear stress exerted by blood flow is crucial for the development and function of the vascular system (1,2). The relaxation of vascular smooth muscle in response to fluid shear stress sensed by the endothelium is a central autoregulatory function of the vessel, which adapts vessel diameter to blood flow and thereby controls vascular tone and blood pressure (3).…”

P2Y2 and Gq/G11 control blood pressure by mediating endothelial mechanotransduction

“…Biophysical evidence indicated that PECAM-1 is not a primary mechanosensor, but that it is controlled by upstream mechanisms that have remained elusive (17,18). Other mechanotransducers suggested to date include mechanosensitive ion channels (19)(20)(21), the endothelial glycocalyx layer (22,23), and the primary cilium (24). Also, pertussis toxin-sensitive and -insensitive heterotrimeric G proteins have been linked with fluid shear stress-induced endothelial signaling (25)(26)(27)(28), and the G proteins G q and G 11 have recently been shown to interact with PECAM-1 and to mediate fluid shear stress-induced AKT phosphorylation (27,28).…”

Endothelial Glycocalyx: Novel Insight into Atherosclerosis

“…It is worth to investigate why high shear stress plays distinct roles in atherosclerotic lesions and normal vessels. High shear stress induced the NO, which subsequently lead to vasodilatation, reducing shear stress [17]. In the lesion location in vessel, a continuous exposure of EC to high shear stress might induced an abnormal increase in NO production, which further induce extracellular matrix and glycocalyx degradation through MMPs [50], as well as inflammation.…”

“…Shear stress induces clustering of the major components of endothelial glycocalyx including glypican-1 with attached heparan sulfate (HS) [11,16]. S1P is a lipid mediator and mostly present in plasma that induces various cellular effects, including proliferation, differentiation, survival, and migration [17]. S1P is also emerging as a potent modulator of endothelial barrier function and vascular tone [18].…”