A novel butyrolactone derivative inhibited smooth muscle cell migration and proliferation and maintained endothelial cell functions through selectively affecting Na, K-ATPase activity and mitochondria membrane potential during in vitro angiogenesis.

We have found that 3-benzyl-5-((2-nitrophenoxy) methyl)-dihydrofuran -2(3H)-one (3BDO), could effectively suppress human umbilical vascular endothelial cell (HUVEC) apoptosis induced by deprivation of fibroblast growth factor-2 and serum. Here, our purpose was to investigate whether 3BDO could modulate angiogenesis and its possible acting mechanism. The effect of 3BDO on angiogenesis was investigated by capillary-like tubule formation and rat aortic ring assay. Proliferation and migration of cells were detected by counting living cell number and scraping cell monolayer, respectively. Na, K-ATPase activity was measured spectrophotometrically. Mitochondrial membrane potential was analyzed using tetramethylrhodamine methylester fluorescence by confocal microscopy. Our results showed that 3BDO inhibited migration and proliferation of vascular smooth muscle cells (VSMCs), but maintained migration and tubule formation of HUVECs. In HUVECs, 3BDO inhibited Na, K-ATPase activity, but had no effect on mitochondria membrane potential. In VSMCs, it did not affect Na, K-ATPase activity, but depressed mitochondria membrane potential obviously. The data showed that 3BDO had selective effects on HUVECs and VSMCs, it might perform its role through the selective effects on the activity of Na, K-ATPase and the mitochondria membrane potential in HUVECs and VSMCs.