Cyclical Strain Increases Endothelin-1 Secretion and Gene Expression in Human Endothelial Cells

Abstract

We examined the effects of cyclical strain on endothelin-1 (Et-1) secretion and Et-1 mRNA levels in human umbilical vein endotheial cells. Cultured endothelial cells grown on a flexible membrane base were deformed by vacuum to 20% of maximum strain, at 60 cycles/min, for various time periods. The rate of Et-1 release from strain- treated cells and their Et-1 mRNA levels were measured. Cells subjected to strain increased their Et-1 secretion into the culture medium from 0.17 ng/hr/10 6 cells to 0.44 ng/hr/10 6 cells. Concomitantly, the Et-1 mRNA levels in strained cells increased 1.4-, 2.1- or 2.6- fold (vs control unstrained cells) after 0.25, 0.5 or 6 hours of strain, respectively. Cells exposed to longer periods of strain (>6 hrs) did not further increase their mRNA expression. Pretreatment with calphostin C, a specific inhibitor of protein kinase C, before straining completely abolished Et-1 mRNA expression. These results indicate that mechanical strain can modulate the secretion of Et-1 from endothelial cells by increasing Et-1 mRNA levels via the protein kinase C pathway. Elevation of Et-1 secretion and gene expression in endothelial cells under physiological strain might influence normal or pathological states of the vasculature and cardiac growth.