Nobel protein on the surface regulates platelet thrombus formation
Researchers of the Catalan Institute of Cardiovascular Sciences (ICCC) have identified a novel antithrombotic mechanism mediated by protein GRP78 platelet surface. We have studied the effect of rosuvastatin, a new lipid lowering drug, on platelet adhesion and location of this protein in platelets.
The aim of the research led by Prof. Lina Badimon, director of the Catalan Institute of Cardiovascular Sciences (ICCC), was to analyze the effect of rosuvastatin on platelet deposition under flow conditions and identify new platelet proteins involved in the interaction with activating substrate, using a proteomic approach.
The study published in Atherosclerosis Thrombosis and Vascular Biology shows that rosuvastatin has an antithrombotic effect and significantly reduces platelet adhesion and activation of the glycoprotein IIb/IIIa. In addition, rosuvastatin keeps GRP78 protein on the surface inhibiting platelet procoagulant activity of tissue factor.
?The proteomic analysis had identified for first time the protein GRP78 on the surface of platelets and had analyzed the effect of the rosuvastatin. The localization of this protein in platelet membrane was confirmed by confocal microscopy" asserts Blanca Molins, first author of the study.
The study demonstrates the important role of this protein in the thrombotic process and its interaction with tissue factor. The GRP78 blocking in platelets produced a substantial increase in platelet adhesion and procoagulant activity, as well as a decrease in time for clot formation.
The results of this research - funded by the Spanish National Health Plan (MICINN), CIBERobn (CIBER of Obesity and Nutrition), AGAUR and the Fundación Jesús Serra - demonstrate that treatment with rosuvastatin reduces platelet deposition and inhibits the translocation of the GRP78 platelet surface in response to activation. The role of GRP78 in the membrane platelet thrombus growth may be mediated by its ability to attenuate the activity of tissue factor or by yet unknown mechanisms that require further study.
This study has described and identified for the first time, the presence and functional role of GRP78 in platelets and indicates that GRP78 has additional functions beyond those of a molecular chaperone membrane. The study suggests that the protein GRP78, an endoplasmic reticulum protein with antiapoptotic properties, processes involved in cancer, could have a protective effect on atherothrombotic disease.
Paper:
GRP78 and Platelet Deposition. Effect of Rosuvastatin.
Molins B, Pena E, Padro T, Casani L, Mendieta C, Badimon L.
Arterioscler Thromb Vasc Biol 2010 April 1.
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Catalan Institute of Cardiovascular Sciences
Hospital de la Santa Creu i Sant Pau, Pavelló del Convent
Sant Antoni Maria Claret, 167 08025 Barcelona
Spain
T: +34 - 93 556 5900 F: +34 - 93 556 5559