REGULATION OF THE FIBRINOLYTIC POTENTIAL OF CULTURED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS - ASTRAGALOSIDE-IV DOWN-REGULATES PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND UP-REGULATES TISSUE-TYPE PLASMINOGEN-ACTIVATOR EXPRESSION
Wj. Zhang et al., REGULATION OF THE FIBRINOLYTIC POTENTIAL OF CULTURED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS - ASTRAGALOSIDE-IV DOWN-REGULATES PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND UP-REGULATES TISSUE-TYPE PLASMINOGEN-ACTIVATOR EXPRESSION, Journal of vascular research, 34(4), 1997, pp. 273-280
We have investigated whether the saponin astragaloside IV (AS-IV), a y
ranosyl-6-O-beta-D-glucopyranosylcycloastragenol, purified from the Ch
inese herb drug Astragalus membranaceus, which is used in traditional
Chinese medicine to treat cardiovascular diseases, might affect the fi
brinolytic potential of cultured human umbilical vein endothelial cell
s (HUVECs). When HUVECs were conditioned with AS-IV, a dose (0.01-100
mu g AS-IV/ml)- and time-dependent decrease in plasminogen activator i
nhibitor type 1 (PAI-1) and an increase in tissue-type plasminogen act
ivator (t-PA) synthesis were observed, which were significant from 1 m
u g AS-IV/ml and from 12 h of incubation with 100 mu g AS-IV/ml. PAI-1
antigen decreased from 641 +/- 86 to 318 +/- 18 ng/10(5) cells/24 h,
whereas t-PA antigen increased from 4.1 +/- 0.3 to 9.7 +/- 0.4 ng/10(5
) cells/24 h after addition of 100 mu g AS-IV/ml. PAI-1 activity decre
ased to 30% of control level, whereas t-PA activity and t-PA-PAI-1 com
plexes reached a maximum stimulation of 3- and 5-fold over control lev
els, respectively, in the conditioned media of HUVECs treated with 100
mu g AS-IV/ml for 24 h. PAI-1-specific mRNA expression decreased to 5
5% (2.2 kb) and 72% (3.2 kb), 66% (2.2 kb) and 88% (3.2 kb), and 19% (
2.2 kb) and 41% (3.2 kb) of control values after incubation for 6, 12
and 18 h, respectively, whereas t-PA-specific mRNA increased 2-, 2.5-
and 1.4-fold in HUVECs treated with 100 mu g/ml AS-IV for 6, 12, and 1
8 h, respectively. In conclusion our data give evidence that in fact A
S-IV can increase the fibrinolytic potential of cultured HUVECs not on
ly by upregulating the expression of t-PA as NG-R1 does, but also by d
ownregulating the expression of PAI-1.