Artery Research

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Volume 16, Issue C, December 2016, Pages 69 - 69

9.5 COAGULATION CONTROL BY THE RHOA PATHWAY AND THE EXCHANGE FACTOR ARHGEF1

Authors
Camille Rouillon1, Amel Mohammadi1, Gervaise Loirand2, Veronique Regnault1, Patrick Lacolley1
1UMR S 1116 Defaillance Cardiovasculaire Aigue et Chronique, Nancy, France
2UMR 1087 Institut du Thorax, Nantes, France
Available Online 24 November 2016.
DOI
10.1016/j.artres.2016.10.072How to use a DOI?
Abstract

Platelet activation by thrombin is an auto-amplification loop of thrombin generation, a major factor in the formation of atherosclerotic plaques. The small G protein RhoA, under the direct control of the exchange factor Arhgef1, modulates several cellular functions in inflammation. The objective was to study the RhoA pathway and its control by Arhgef1 in platelet aggregation and thrombin generation due to PAR receptor activation by thrombin.

We used a knockout mouse model for the exchange factor Arhgef1 (Arhgef1 −/−). In response to an agonist (collagen, ADP and thrombin), the expression of surface glycoproteins and the aggregation of washed platelets were not altered in the Arhgef1 −/− mice compared to Argef1 +/+ mice. In contrast, platelet activation studied by the secretion of granules a, exposure to phosphatidylserine and release of microparticles were decreased in the Arhgef1 −/− mice. Thrombin generation in whole platelet-rich blood was also reduced by 25%. These changes result in a lengthening of the time of occurrence of an occlusive thrombus in the carotid induced by FeCl3.

In conclusion, the results confirm the involvement of the RhoA pathway in platelet activation and demonstrate an Arhgef1-dependent mechanism. The results in mice show a new auto-amplification mechanism of thrombin generation by platelets through PAR and membrane phospholipids. Redistribution of phospholipid linked rearrangements of the membrane complex induced by inflammation suggests that the RhoA pathway potentiates the deleterious effects of thrombin in atherothrombosis.

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This is an open access article distributed under the CC BY-NC license.

References

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Journal
Artery Research
Volume-Issue
16 - C
Pages
69 - 69
Publication Date
2016/11/24
ISSN (Online)
1876-4401
ISSN (Print)
1872-9312
DOI
10.1016/j.artres.2016.10.072How to use a DOI?
Open Access
This is an open access article distributed under the CC BY-NC license.

Cite this article

risenwbib
TY  - JOUR
AU  - Camille Rouillon
AU  - Amel Mohammadi
AU  - Gervaise Loirand
AU  - Veronique Regnault
AU  - Patrick Lacolley
PY  - 2016
DA  - 2016/11/24
TI  - 9.5 COAGULATION CONTROL BY THE RHOA PATHWAY AND THE EXCHANGE FACTOR ARHGEF1
JO  - Artery Research
SP  - 69
EP  - 69
VL  - 16
IS  - C
SN  - 1876-4401
UR  - https://doi.org/10.1016/j.artres.2016.10.072
DO  - 10.1016/j.artres.2016.10.072
ID  - Rouillon2016
ER  -