Proliferation and anti-apoptotic effects of human urotensin II on human endothelial cells

Background Human urotensin II (hU-II) is a potent vasoconstrictor, highly expressed in cardiac tissues and blood vessels. Recent studies indicate that hU-II participates in vascular and myocardial remodeling after injury. This study was designed to study the role of hU-II in cell DNA synthesis and apoptosis in human umbilical vein endothelial cells (HUVECs) and underlying intracellular signaling mechanisms. Methods and Results Cultured HUVECs were incubated with hU-II (10−10–10–8 M) for 24 h. Cell DNA synthesis was examined by 3H thymidine incorporation. Apoptosis was detected by flow cytometry and TUNEL. hU-II increased the 3H thymidine incorporation into DNA in a concentration-dependent manner. hU-II inhibited endothelial apoptosis induced by serum withdrawal (5.74 ± 0.64% versus 13.20 ± 1.96%, P < 0.01) and TNFα (6.76 ± 0.70% versus 13.80 ± 1.02%, P < 0.01). The data from flow cytometry and TUNEL are consistent. Further studies showed that hU-II caused the phosphorylation of mitogen-activated protein kinasep42/44 (MAPKp42/44) in a concentration-dependent manner and this effect of hU-II was inhibited by pretreatment of cells with the MEK inhibitor (PD98059, 10 μM). In addition, the use of PD98059 also attenuated 3H thymidine incorporation and anti-apoptotic effect elicited by hU-II (both P < 0.01 versus hU-II alone). Conclusions Our observations provide evidence that hU-II promotes cell proliferation and inhibits apoptosis in HUVECs, and MAPKp42/44 activation may play a signal transduction role in this process.