Both Senescence and Apoptosis Induced by Deprivation of Growth Factors Were Inhibited by a Novel Butyrolactone Derivative through Depressing Integrin β4 in Vascular Endothelial Cells

Abstract

Both senescence and apoptosis of vascular endothelial cells (VECs) are involved in the development of cardiovascular diseases, including atherosclerosis. To understand the association between senescence and apoptosis in vascular endothelial cells, the authors first explored whether senescence and apoptosis took place at the same time in human umbilical vein endothelial cells (HUVECs) deprived of the growth factors. Integrin beta4 is a key factor in HUVEC apoptosis, to know whether this integrin is implicated in VEC senescence, the authors checked the changes of integrin beta4 level during HUVEC aging. Then the authors investigated the effects of 3BDO (3-benzyl-5-((2-nitrophenoxy)methyl)-dihydrofuran-2(3H)-one) on the senescence induced by deprivation of serum and fibroblast growth factor (FGF)-2. The results showed that deprivation of growth factors not only induced apoptosis, but also triggered senescence in HUVECs. The authors found that the level of integrin beta 4 was increased markedly during HUVEC senescence. 3BDO (20 to 60 microg/mL) could inhibit both senescence and apoptosis and depress integrin beta 4 level. The data suggested that integrin beta4 might be a pivotal factor in the relationship between senescence and apoptosis.