Arterial shear stress stimulates surface expression of the endothelial glycoprotein Ib complex

Abstract

Exposure to shear stress has been shown to alter the expression of a number of surface components of cultured endothelial cells (EC). However, relatively few studies have examined the status of human EC surface proteins after prolonged flow, more closely corresponding to the steady state in vivo. Since the promoter region of glycoprotein (Gp) Ib alpha contains several copies of a putative shear stress response element, 5'-GAGACC-3', we investigated the response of cultured human umbilical vein EC (HUVEC) GpIb alpha to shear stress over a 72 h time period. In response to 30 dynes/cm2 of shear stress, total cell content of GpIb alpha protein was markedly increased above static levels at 7 and 24 h, as determined immunohistochemically. Western blot analysis of whole cell lysates after 24, 48, and 72 h of shear treatment demonstrated a 2.4-, 4.1-, and 3.2-fold increase in total GpIb alpha protein, respectively. Cell surface protein expression of GpIb alpha increased 2.5-fold at 7 h, as measured by quantitative immunofluorescence, and remained at that level at 24 h. After 48 h of shear stress, cell surface GpIb alpha, GpIX, and GpV, analyzed by flow cytometric analysis, were further increased over the levels observed at 24 h. The increase in cell surface membrane expression of GPIb alpha at 24, 48, and 72 h was confirmed by immunoprecipitation of biotinylated surface proteins. No upregulation of GpIb alpha was noted after exposure to shear stress of 1-3 dynes/cm2. These observations imply that under steady-state arterial shear conditions endothelial expression of the GpIb complex is significantly greater than observed in static EC cultures, and raise the possibility of a more important role for this complex under flow, rather than static conditions.

Thrombospondin‐1 mediates platelet adhesion at high shear via glycoprotein Ib (GPIb): an alternative/backup mechanism to von Willebrand factor

“…Several cells express TSP-1 or bind TSP-1 to their surfaces, when they are activated, like platelets, monocytes, T-cells, endothelial cells, and many tumor cells (4). Arterial shear stress stimulates surface expression of the endothelial GPIb complex and VWF binding to GPIb in platelets (44). The newly discovered GPIb-TSP-1 adhesion axis under arterial shear conditions might be important, not only during thrombus formation but also for pathological processes, including arteriosclerosis and tumor metastasis, where other cells bind to the endothelium.…”

Acquired von Willebrand Syndrome: Experience from 2 Years in a Single Laboratory Compared with Data from the Literature and an International Registry

“…The stimulatory effect of high shear stress rates on endothelial cells has been addressed in the literature. 46,47 The high level of vWF stabilizes the FVIIIc molecule, effectively leading to a parallel rise of the FVIII activity and an increase in the risk for venous thrombosis, a situation that is much more common at higher ages. 48 The possible involvement of high vWF concentrations in arterial disease states is less well-documented but nevertheless feasible.…”

Glycobiology of platelet-endothelial cell interactions

“…Endothelial cells also express PSGL-1 and the glycoprotein Ibα, which mediate tethering and firm adhesion of activated platelets (P-selectin-expressing cells) to the endothelium (Beacham et al 1999;Tan et al 1999;da Costa Martins et al 2007). Other P-selectin ligands present on endothelial cells are glycosylationdependent cell adhesion molecule-1 (Koenig et al 1997) and endoglycan (a member of the CD34 family of sialomucins) (Kerr et al 2008); the expression of these molecules could also mediate the interaction of the endothelium with platelet P-selectin.…”