Angiotensin-(1-7) modulates fibrinolytic imbalance induced by oxidized low-density lipoprotein in cultured human umbilical vein endothelial cells

Abstract

Abstract: Objective To study the effect of angiotensin-(1-7)[Ang-(1-7)]on fibrinolytic imbalance induced by oxidized low-density lipoprotein (ox-LDL) in cultured human umbilical vein endothelial cells (HUVECs). Method Cultured HUVECs were incubated for 24 h in the presence of Ang-(1-7), ox-LDL and A-779 at different concentrations either separately or in combination. The final concentrations of Ang-(1-7) were 10, 100 and 1 000 nmol/L, and those of ox-LDL were 25, 50 and 100 mg protein/L. The final concentration of A-779, an Ang-(1-7) receptor antagonist, was 100 nmol/L. Tissue plasminogen activator (t-PA) and its inhibitor-1(PAI-1) antigen in the medium were determined by enzyme-linked immunosorbent assay (ELISA) and their mRNA levels by reverse transcriptional (RT) PCR. Results Ox-LDL (25-100 mg protein/L) dose-dependently increased PAI-1 release and up-regulated PAI-1 gene transcription, but decreased t-PA release and down-regulated t-PA gene transcription (P<0.001-0.05). Ang-(1-7) (100-1 000 nmol/L) dose-dependently decreased PAI-1 release and PAI-1 gene transcription (P<0.01-0.05) but had no effect on t-PA release and gene transcription. In the presence of ox-LDL, Ang-(1-7) lowered the increased levels of PAI-1 and PAI-1 mRNA, and elevated the levels of decreased t-PA and t-PA mRNA in the cells (P<0.01-0.05). The effects of Ang-(1-7) could be blocked by A-779. Conclusion Angiotensin-(1-7) effectively modulates the fibrinolytic imbalance induced by ox-LDL via its specific receptor.

CLC Number:

R394.2

WANG Li-jun, MA Hong, CAI Yi-ming, HE Jian-gui, LIAO Xin-xue, ZENG Wu-tao, WANG Li-chun, LIU Jun. Angiotensin-(1-7) modulates fibrinolytic imbalance induced by oxidized low-density lipoprotein in cultured human umbilical vein endothelial cells[J]. Journal of Southern Medical University, 2005, 25(06): 633-637.

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