Endothelin-1 and Endothelin-Converting Enzyme-1 Gene Regulation by Shear Stress and Flow-Induced Pressure

Abstract

Hemodynamic forces have been shown to modulate the expression of endothelin (ET-1) and endothelin-converting enzyme (ECE-1) in endothelial cells. We have subjected E.A. hy 926 cells in culture to steady fluid shear stress with and without flow-induced pressure. The effect of combining these two mechanical forces on the expression of genes in the ET system was studied and the changes were compared to the mRNA levels in static culture. Analysis of total RNA by Northern blot analysis and RNAse protection showed that steady shear stress induced ET-1 gene expression three- to fourfold in this system. The same condition had little to no effect on altering expression of ECE-1 isoforms. A range of flow-induced pressure (80-160 mm Hg) was not able to further augment ET-1 or ECE-1 gene expression. Overall, with the mechanical environment studied, we have been able to detect a predominant contribution of shear stress to altering the ET-1 gene in our system. Furthermore, this induction was independent of an alteration of ECE-1 gene levels, suggesting that these two genes have a different pattern of regulation by the same stimuli in this cell type.

Cap G, a Gelsolin Family Protein Modulating Protective Effects of Unidirectional Shear Stress

“…Recently, the importance of the hemody- namic forces on ECs has become evident, both at the level of cell morphology as well as at the level of gene expression (1, 4). Moreover, it has been demonstrated that different hemodynamic conditions reproduced in in vitro experiments induce opposite effect on ECs, particularly in the context of endothelial nitric-oxide synthase, vascular cell adhesion molecule-1, and growth factor gene expression (5,6,8,26). All of these data suggest that unidirectional flow, typical of plaque-free areas, exerts a "protective" effect on endothelial cells.…”

Emergence of Smooth Muscle Cell Endothelin B–Mediated Vasoconstriction in Lambs With Experimental Congenital Heart Disease and Increased Pulmonary Blood Flow

“…Although increasing in vitro data suggest that changes in mechanical forces alter ET-1 signaling, few data are available on the regulation of ET receptor signaling. 23,24 Therefore, the potential mechanisms for the current receptor changes are unknown and warrant further investigation.…”

Flow-Induced Pressure Differentially Regulates Endothelin-1, Urotensin II, Adrenomedullin, and Relaxin in Pulmonary Vascular Endothelium

“…First, Hishikawa et al reported that pure pressure up to 160 mm Hg without flow increases ET-1 release from umbilical vein endothelial cells and that this effect is mediated by phospholipase C and protein kinase C pathways (24). Second, Harrison et al found no effect of flow-induced pressure (80 -160 mm Hg) on ET-1 and ECE-1 in E. A. hy 926 cells (25). In our study, we attempted to mimic the in vivo situation in pulmonary circulation as closely as possible, which included the selection of pulmonary cells as well as the application of flow-related pressures and shear stresses that reflect in vivo data (4,13,14).…”