AGING-DEPENDENT AND GROWTH-DEPENDENT MODULATION OF ENDOTHELIN-1 GENE-EXPRESSION IN HUMAN VASCULAR ENDOTHELIAL-CELLS

Earlier we reported the undetectable level of endothelin (ET)-1 mRNA i n aorta from young donors, in contrast to the detectable levels in old er donors (Lab. Invest. 67, 210-217, 1992). We also found that the syn thesis of ET-1 peptide is elevated in cultured endothelial cells from the aorta of over-50-year-old donors. In the present report, we show b y in situ hybridization that the level of ET-1 mRNA is not so differen t in aortic endothelial cells from 5- and 50-year-old donors, but incr eases in cells from 76-year-old donors. The parallel results are obtai ned from Northern and in situ hybridization analyses by using serially passaged human umbilical vein endothelial cells. Thus, the increase o f ET-1 peptide synthesis is achieved mainly at the level of mRNA. Furt hermore, these results suggest that the increased expression of ET-1 i n elderly people is due to the exhaustion of cell division potential o f endothelial cells in vivo. We have also analyzed whether the express ion of ET-1 is affected by the growth state. The data show that sparse ly growing cells secrete more ET peptide than confluent and stationary cells. In situ hybridization also shows that S-phase cells express mo re ET-1 mRNA than non-S-phase cells. Thus, it is suggested that there are, at least, two ways for upregulation of ET-1 expression. (C) 1994 Academic Press, Inc.