Effect of angiotensin II on tissue factor expression in human peripheral blood monocytes and its mechanisms / 中华血液学杂志
Chinese Journal of Hematology
;
(12): 470-473, 2003.
Article
in Chinese
| WPRIM
| ID: wpr-354850
ABSTRACT
<p><b>OBJECTIVE</b>To elucidate the effect of angiotensin II (AngII) on the expression of tissue factor (TF) by monocytes and its mechanisms.</p><p><b>METHODS</b>Monocytes were isolated from healthy volunteers by Ficoll-Hypaque gradient and Percoll, and cultured in RPMI-1640. Procoagulant activity (PCA) was determined by one-stage clotting method, TF antigen by ELISA. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the TF gene mRNA. The levels of IkappaBalpha was detected by Western blot. Electrophoretic mobility shift assays (EMSA) were performed to evaluate the activity of NF-kappaB.</p><p><b>RESULTS</b>AngII (10(-9) - 10(-7) mol/L) significantly increased monocyte PCA, TF antigen and TF mRNA expression in a dose and time dependent manner. Losartan (10(-6) - 10(-5) mol/L) significantly inhibited the effects of AngII on TF activity, antigen and mRNA expression in a dose-dependent effects. Staurosporine (2.5 x 10(-7) mol/L) and genistein (4 x 10(-5) mol/L) lowered TF level of monocytes (P < 0.05). Western blot analysis revealed that after exposure to AngII (10(-7) mol/L), IkappaBalpha level decreased at 15 min, reached nadir at 60 min, and recovered at 180 min. EMSA showed NF-kappaB binding activity increased at 15 min, reached peak at 60 min, and recovered at 180 min. Pyrrolidine dithiocarbamate (PDTC, 10(-4) mol/L), an inhibitor of NF-kappaB, or AT1R antagonist losartan (10(-5)mol/L) inhibited AngII-induced NF-kappaB translocation.</p><p><b>CONCLUSIONS</b>AngII could induce the expression of TF in human monocytes, and this effect was mediated by AT1R. The PKC pathway played the most important role in AngII-induced TF expression. The activation of NF-kappaB was involved in TF expression in monocytes.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Physiology
/
Protein Kinase C
/
RNA, Messenger
/
Thromboplastin
/
Angiotensin II
/
Monocytes
/
Gene Expression Regulation
/
NF-kappa B
/
Staurosporine
Limits:
Humans
Language:
Chinese
Journal:
Chinese Journal of Hematology
Year:
2003
Type:
Article
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