Shear-Induced Changes in Endothelin-1 Secretion of Microvascular Endothelial Cells

Abstract

Human glomerular microvascular endothelial cell (HGMEC) culture monolayers were maintained in static culture as controls or subjected to steady laminar shear stress of 0.5, 1.0, or 1.5 N/m2. Over 25 h of shear, the cumulative secretion of ET-1 was 705.4 pg/cm2 in the control, 820.7 pg/cm2 at 0.5 N/m2, 1063.2 pg/cm2 at 1.0 N/m2, and 644.7 pg/cm2 at 1.5 N/m2. The average ET-1 secretion rate for the HGMEC monolayers exposed to 0.5, 1.0, or 1.5 N/m2 of shear stress was 32.83 ± 2.01 pg/cm2·h, 42.53 ± 3.74 pg/cm2·h, and 25.79 ± 1.29 pg/cm2·h, respectively. The average ET-1 secretion rate of the static controls was 28.22 ± 3.11 pg/cm2·h. The results showed that low shear stress (0.5 N/m2) elevated and high shear stress (1.5 N/m2) suppressed secretion of ET-1, while an intermediate level of shear stress (1.0 N/m2) led to the maximum secretion of ET-1, and furthermore, ET-1 secretion varied with the duration of shear in a nonlinear fashion, and the logistic equations may be used to describe relationship between the duration of shear and the ET-1 secretion. The major secretion period of ET-1 occurred between 5.3 and 22.3 h, with the peak secretion rate occurring at approximately 10.7–15.2 h. Our findings showed also that the major secretion period and peak secretion rate of HGMECs varied with the level of shear stress. Thus, the response of cultured human microvascular endothelial cells to shear stress differed from that of large-vessel endothelial cell cultures in terms of ET-1 secretion. In addition to the level of shear stress, the duration of shear is an important determinant in ET-1 secretion. Consequently, the heterogeneity of vascular endothelial cells and the duration of shear should both be considered in future research on the secretion of vascular endothelial cell cultures.