Activated protein C induction of MCP-1 in human endothelial cells: a possible role for endothelial cell nitric oxide synthase.
Thromb Res
; 103(3): 209-19, 2001 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-11672583
ABSTRACT
Classically, activated protein C (APC) of the protein C/protein S anticoagulant pathway has functioned not only to inactivate the procoagulant factors Va and VIIIa but also to inhibit the activity of plasminogen activator inhibitor-1 (PAI-1). More recent data have suggested that the protein C/protein S pathway may serve as a physiological link between coagulation and inflammation. This APC pathway link was proposed because of observations showing that APC could both modulate the effects of cytokines and block neutrophil activation. As a further extension of the effect(s) of APC on cytokines, we found that APC, at the equivalent physiological protein C concentration of 4 microg/ml, significantly upregulated monocyte chemotactic protein-1 (MCP-1) RNA in human umbilical vein endothelial cells (HUVECs), as indicated by a ribonuclease protection assay (RPA) at 3 and 6 h with a return to near basal levels by 24 h. ELISA determinations demonstrated that 4 microg/ml of APC induced a significant (P=.0001) increase in MCP-1 protein production over basal levels within a 24-h period. At the same concentration, APC downregulated endothelial cell nitric oxide synthase (eNOS) RNA. Downregulation first became apparent at 6 h and continued through 48 h of culture. This downregulation was concentration dependent over a range of 1.3-12 microg/ml, and there was no effect on cell viability within this range. In support of other studies, we also found that exogenously added nitric oxide (NO) inhibited MCP-1 production. These data suggest that APC may induce MCP-1 through the inhibition of eNOS.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína C
/
Endotelio Vascular
/
Quimiocina CCL2
/
Fibrinolíticos
Límite:
Humans
Idioma:
En
Revista:
Thromb Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Estados Unidos