Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI
| العنوان: | Human atheromatous plaques stimulate thrombus formation by activating platelet glycoprotein VI |
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| المؤلفون: | Bernd Engelmann, Bernhard Nieswandt, Peter A. Smethurst, Richard Brandl, Sandra M Penz, Richard W. Farndale, Armin J. Reininger, Isabell Bernlochner, Pankaj Goyal, Tamer Rabie, Wolfgang Siess, Enno Rother, Christine A. Goetz, Willem H. Ouwehand |
| المصدر: | The FASEB Journal. 19:898-909 |
| بيانات النشر: | Wiley, 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Blood Platelets, Pathology, medicine.medical_specialty, Platelet Aggregation, Thrombogenicity, Platelet Membrane Glycoproteins, Biochemistry, Collagen Type I, Monocytes, Mice, Tissue factor, Platelet Adhesiveness, Platelet adhesiveness, Genetics, medicine, Animals, Humans, Carotid Stenosis, Platelet, Platelet activation, Thrombus, Blood Coagulation, Molecular Biology, Chemistry, Thrombosis, Atherosclerosis, Platelet Activation, medicine.disease, Lipids, Collagen Type III, Microscopy, Fluorescence, Coagulation, Immunology, Integrin alpha2beta1, GPVI, Biotechnology |
| الوصف: | Lipid-rich atherosclerotic plaques are vulnerable, and their rupture can cause the formation of a platelet- and fibrin-rich thrombus leading to myocardial infarction and ischemic stroke. Although the role of plaque-based tissue factor as stimulator of blood coagulation has been recognized, it is not known whether plaques can cause thrombus formation through direct activation of platelets. We isolated lipid-rich atheromatous plaques from 60 patients with carotid stenosis and identified morphologically diverse collagen type I- and type III-positive structures in the plaques that directly stimulated adhesion, dense granule secretion, and aggregation of platelets in buffer, plasma, and blood. This material also elicited platelet-monocyte aggregation and platelet-dependent blood coagulation. Plaques exposed to flowing blood at arterial wall shear rate induced platelets to adhere to and spread on the collagenous structures, triggering subsequent thrombus formation. Plaque-induced platelet thrombus formation was observed in fully anticoagulated blood (i.e., in the absence of tissue factor-mediated coagulation). Mice platelets lacking glycoprotein VI (GPVI) were unable to adhere to atheromatous plaque or form thrombi. Human platelet thrombus formation onto plaques in flowing blood was completely blocked by GPVI inhibition with the antibody 10B12 but not affected by integrin alpha2beta1 inhibition with 6F1 mAb. Moreover, the initial platelet response, shape change, induced by plaque was blocked by GPVI inhibition but not with alpha2beta1 antagonists (6F1 mAb or GFOGER-GPP peptide). Pretreatment of plaques with collagenase or anti-collagen type I and anti-collagen type III antibodies abolished plaque-induced platelet activation. Our results indicate that morphologically diverse collagen type I- and collagen type III-containing structures in lipid-rich atherosclerotic plaques stimulate thrombus formation by activating platelet GPVI. This platelet collagen receptor, essential for plaque-induced thrombus formation, presents a promising new anti-thrombotic target for the prevention of ischemic cardiovascular diseases. |
| تدمد: | 1530-6860 0892-6638 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::109b3357bffc7fd3f058aefe6b228ee0 https://doi.org/10.1096/fj.04-2748com |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....109b3357bffc7fd3f058aefe6b228ee0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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