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Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells.

Authors :
Rodgers GM
Conn MT
Source :
Blood [Blood] 1990 Feb 15; Vol. 75 (4), pp. 895-901.
Publication Year :
1990

Abstract

Elevated blood levels of homocysteine are associated with atherosclerosis and thrombotic disease. We previously reported that treatment of cultured endothelial cells with homocysteine increased endogenous factor V activity by activation of the cofactor. Because endothelial cell-associated factor Va would be regulated by the protein C mechanism, the ability of homocysteine-treated arterial and venous endothelial cells to activate protein C was investigated. Both arterial and venous endothelial cells activated protein C; 0.6 mmol/L homocysteine reduced endothelial cell protein C activation by 12%. Maximal inhibition (90%) of protein C activation occurred with 7.5 to 10 mmol/L homocysteine after 6 to 9 hours of incubation. Metabolism of homocysteine was not accelerated by cultured endothelial cells. Investigation of the mechanism(s) by which homocysteine reduced protein C activation indicated that the metabolite did not induce an inhibitor to activated protein C, but in low concentrations acted as a competitive inhibitor to thrombin. These data suggest that perturbation of the vascular endothelial cell protein C mechanism by homocysteine may contribute to the thrombotic tendency seen in patients with elevated blood levels of this metabolite.

Details

Language :
English
ISSN :
0006-4971
Volume :
75
Issue :
4
Database :
MEDLINE
Journal :
Blood
Publication Type :
Academic Journal
Accession number :
2154269