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

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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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  -