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.


RESULTS
Cultured HUVECs were incubated with hU-II (10(-10)-10(-8)M) for 24h. 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 TNFalpha (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, 10muM). 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.
Shi
Libin
L
Division of Cardiology, Department of Internal Medicine, Peking University First Hospital, Xishiqudaji #8, West district, Beijing 100034, China.
Ding
Wenghui
W
Li
Dayuan
D
Wang
Zhijian
Z
Jiang
Hongfeng
H
Zhang
Junhua
J
Tang
Chaoshu
C
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*; D014470:Umbilical Cord / Q000166:cytology; D014579:Urotensins / Q000494:pharmacology*
D014579:Urotensins; C029677:urotensin II; D019950:Mitogen-Activated Protein Kinase 1