Modulation of gene expression during aging of human vascular endothelial cells

Vascular endothelial cells are thought to play an important role in human aging as their senescence and detachment from a vascular wall may contribute to arteriosclerosis and high blood pressure in the elderly. We investigated the level of fibronectin (FN) expression in aortic endothelial cells aged in vivo, because FN is necessary for cell attachment and spreading and its increased expression had been shown in aging fibroblasts. The results showed that the steady state level of expression of FN mRNA increased with advancing donor age, while the labeling index of cultured cells decreased with age. Furthermore, the increased level of FN expression clearly correlated with an increase in cell area. In order to explore whether these changes reflected exhaustion of proliferation potential in vivo, we examined FN expression in human umbilical vein endothelial (HUVE) cells aging in vitro. Very similar results were obtained, supporting the idea that vascular endothelial cells age in vivo by using up division potential. Furthermore, we investigated the level of endothelin (ET) -1 mRNA expression during in vitro cellular aging of HUVE cells. The results showed that the expression of ET-1 gene was also up-regulated when the culture became old. It is very interesting that the genes for quite different proteins of FN and ET-1 are both up-regulated during cellular aging.