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


METHODS
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.


CONCLUSIONS
Angiotensin-(1-7) effectively modulates the fibrinolytic imbalance induced by ox-LDL via its specific receptor.
Wang
Li-jun
LJ
Department of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China. wanglj63@163.com
Ma
Hong
H
Cai
Yi-ming
YM
He
Jian-gui
JG
Liao
Xin-xue
XX
Zeng
Wu-tao
WT
Wang
Li-chun
LC
Liu
Jun
J
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis* / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology
C092006:7-Ala-angiotensin (1-7); D057911:Angiotensin Receptor Antagonists; D008077:Lipoproteins, LDL; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C099252:oxidized low density lipoprotein; D000804:Angiotensin II; D000803:Angiotensin I; D010959:Tissue Plasminogen Activator; C118790:angiotensin I (1-7)