Glucose-Regulated Protein and Platelet Deposition. Effect of Rosuvastatin.
2010, Arterioscler Thromb Vasc Biol. 2010 Apr 1. [Epub ahead of print]
Molins B, Peña E, Padro T, Casani L, Mendieta C, Badimon L.
Autors del centre relacionats: Badimon Lina, Casaní Laura, Padró Teresa, Peña Esther.
Molins B, Peña E, Padro T, Casani L, Mendieta C, Badimon L.
Autors del centre relacionats: Badimon Lina, Casaní Laura, Padró Teresa, Peña Esther.
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau,Barcelona, Spain; Ciber Patofisiologia de la Obesidad y Nutricion, Institute Carlos III; and Periodontics Department, Faculty of Odontology, University of Barcelona, Barcelona, Spain.
Abstract
OBJECTIVE: To investigate the effect of rosuvastatin on platelet deposition under controlled shear rate conditions and to identify new platelet proteins involved in the interaction with the activating substrate. METHODS AND RESULTS: Platelet-vessel wall interaction and thrombosis take place under dynamic conditions involving the interaction of the exposed damaged vascular wall with the circulating blood cells and proteins. Blood was perfused over type I collagen at different wall shear rates, and platelet deposition was measured by confocal microscopy. Perfused effluent blood was collected, platelets were sequentially extracted based on differential protein solubility, and proteins were separated by 2D gel electrophoresis. Blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase significantly reduced platelet deposition and modulated the expression pattern of 18 proteins in the platelet subproteome. Among them, an increase in platelet surface 78-kDa glucose-regulated protein (GRP78), a stress-inducible multifunctional endoplasmic reticulum protein, was clearly apparent. Immunoprecipitation of platelet GRP78 revealed its interaction with tissue factor. Moreover, blockade of surface GRP78 resulted in a substantial increase in platelet deposition and tissue factor procoagulant activity and in a decrease in clotting time. CONCLUSIONS: These findings demonstrate that blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase reduces platelet deposition and inhibits GRP78 translocation from the platelet surface after shear and collagen activation. For the first time to our knowledge, this study reports on the presence and functional role of GRP78 in platelets and indicates that GRP78 has additional functions beyond those of a molecular chaperone.
PMID: 20360535 [PubMed - as supplied by publisher]
Abstract
OBJECTIVE: To investigate the effect of rosuvastatin on platelet deposition under controlled shear rate conditions and to identify new platelet proteins involved in the interaction with the activating substrate. METHODS AND RESULTS: Platelet-vessel wall interaction and thrombosis take place under dynamic conditions involving the interaction of the exposed damaged vascular wall with the circulating blood cells and proteins. Blood was perfused over type I collagen at different wall shear rates, and platelet deposition was measured by confocal microscopy. Perfused effluent blood was collected, platelets were sequentially extracted based on differential protein solubility, and proteins were separated by 2D gel electrophoresis. Blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase significantly reduced platelet deposition and modulated the expression pattern of 18 proteins in the platelet subproteome. Among them, an increase in platelet surface 78-kDa glucose-regulated protein (GRP78), a stress-inducible multifunctional endoplasmic reticulum protein, was clearly apparent. Immunoprecipitation of platelet GRP78 revealed its interaction with tissue factor. Moreover, blockade of surface GRP78 resulted in a substantial increase in platelet deposition and tissue factor procoagulant activity and in a decrease in clotting time. CONCLUSIONS: These findings demonstrate that blockade of 3-hydroxy-3-methylglutaryl-coenzyme A reductase reduces platelet deposition and inhibits GRP78 translocation from the platelet surface after shear and collagen activation. For the first time to our knowledge, this study reports on the presence and functional role of GRP78 in platelets and indicates that GRP78 has additional functions beyond those of a molecular chaperone.
PMID: 20360535 [PubMed - as supplied by publisher]
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