Signal transduction pathways in vascular cells exposed to cyclic strain

Summary

The importance of external physical forces in influencing the biology of cells is just being realised. Recent reports demonstrate that exposure of endothelial cells (EC) to a flowing culture media or to repetitive elongation can result in changes in morphology, proliferation and secretion of macromolecules (Dewey et al., 1981; Davies et al., 1984; Frangos, Eskin & McIntire, 1985; Sumpio et al., 1987; Diamond, Eskin & McIntire, 1989; Sumpio & Widmann, 1990; Iba & Sumpio, 1991, 1992). Now, the major impetus in the field is to define the ‘mechanosensor(s)’ on the cells that are sensitive to the different external forces, the coupling intracellular pathways and the subsequent nuclear events which precede the cell response.

Mechanosensors

Cell surface sensors

The cell's plasma membrane, besides serving as a barrier to protect the cell interior, is the site of action and translation of external to internal signals. Although no ‘strain-receptor’ as such has been identified, it is clear that endothelial cells can ‘sense’ changes in pressure and strain. Furthermore, it is likely that this ‘sensor’ is located on the cell surface. The endothelial cell surface consists of multiple projections covered by a thin layer of glycocalyx (consisting mainly of glycoproteins, proteoglycans and derived substances). In an effort to characterise possible cell surface sensors, Suarez & Rubio (1991) perfused isolated guinea pig hearts with concavalin A or heparinase (agents which modify endothelial cell surface glycoproteins) and attenuated both the flow and pressure stretch induced rise in glycolytic flux normally seen in guinea pig hearts, while having no effect on basal glycolytic values.