P2.04: Paradoxical Involvement of the Endothelial Mineralocorticoid Receptor in Platelet Activation and Vascular Thrombosis in Mouse
Our aim was to investigate whether mineralocorticoid receptor (MR) over-expression in the vascular endothelium modifies the in vitro thrombin generation using thrombography and enhances the thrombotic risk in vivo . We used our mouse model with conditional overexpression of the MR in endothelial cel...
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Published in | Artery research Vol. 5; no. 4; pp. 153 - 154 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
Dordrecht
Springer Netherlands
2011
Springer Nature B.V BMC |
Subjects | |
Online Access | Get full text |
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Summary: | Our aim was to investigate whether mineralocorticoid receptor (MR) over-expression in the vascular endothelium modifies the
in vitro
thrombin generation using thrombography and enhances the thrombotic risk
in vivo
. We used our mouse model with conditional overexpression of the MR in endothelial cells (MR-EC) (Nguyen Dinh Cat et al, FASEB J. 2010;24:2454–63).
The plasma level of von Willebrand factor was significantly increased in 3 month-old MR-EC mice compared with that in control mice (CT). In the presence of the activated protein C (APC) anticoagulant system, thrombin generation was lower in the plasma of MR-EC mice than in CT. Maximal platelet aggregation in response to collagen was lower in MR-EC than in CT. To address the role of endothelial cells as cellular surfaces involved in the coagulation process,
in vitro
thrombin generation was assessed at the surface of cultured human aortic endothelial cells. Treatment of these cells with 10
−8
Maldosterone resulted in a significant reduction of thrombin generation prevented by the MR antagonist RU28318.
In vivo
, vessel occlusion times after exposure of the carotid artery surface to ferric chloride was delayed in MR-EC compared with CT mice.
These results demonstrated that enhanced endothelial MR activation induced endothelial dysfunction. Paradoxically, MR-EC mice exhibited a decreased risk of thrombosis. Our results suggested that MR activation in the endothelium affected coagulation by enhancing the APC anticoagulant system and decreasing platelet aggregation. This finding raised interesting prospects on the potential mechanisms of action of new anti-thrombotic drugs and their interference with the mineralocorticoids. |
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ISSN: | 1872-9312 1876-4401 1876-4401 |
DOI: | 10.1016/j.artres.2011.10.025 |