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Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels
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| Zeitschriftentitel: | Blood |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , , , , , , , |
| In: | Blood, 119, 2012, 18, S. 4311-4320 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society of Hematology
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| Schlagwörter: |
| author_facet |
Al-Tamimi, Mohammad Tan, Chee Wee Qiao, Jianlin Pennings, Gabrielle J. Javadzadegan, Ashkan Yong, Andy S. C. Arthur, Jane F. Davis, Amanda K. Jing, Jing Mu, Fi-Tjen Hamilton, Justin R. Jackson, Shaun P. Ludwig, Andreas Berndt, Michael C. Ward, Christopher M. Kritharides, Leonard Andrews, Robert K. Gardiner, Elizabeth E. Al-Tamimi, Mohammad Tan, Chee Wee Qiao, Jianlin Pennings, Gabrielle J. Javadzadegan, Ashkan Yong, Andy S. C. Arthur, Jane F. Davis, Amanda K. Jing, Jing Mu, Fi-Tjen Hamilton, Justin R. Jackson, Shaun P. Ludwig, Andreas Berndt, Michael C. Ward, Christopher M. Kritharides, Leonard Andrews, Robert K. Gardiner, Elizabeth E. |
|---|---|
| author |
Al-Tamimi, Mohammad Tan, Chee Wee Qiao, Jianlin Pennings, Gabrielle J. Javadzadegan, Ashkan Yong, Andy S. C. Arthur, Jane F. Davis, Amanda K. Jing, Jing Mu, Fi-Tjen Hamilton, Justin R. Jackson, Shaun P. Ludwig, Andreas Berndt, Michael C. Ward, Christopher M. Kritharides, Leonard Andrews, Robert K. Gardiner, Elizabeth E. |
| spellingShingle |
Al-Tamimi, Mohammad Tan, Chee Wee Qiao, Jianlin Pennings, Gabrielle J. Javadzadegan, Ashkan Yong, Andy S. C. Arthur, Jane F. Davis, Amanda K. Jing, Jing Mu, Fi-Tjen Hamilton, Justin R. Jackson, Shaun P. Ludwig, Andreas Berndt, Michael C. Ward, Christopher M. Kritharides, Leonard Andrews, Robert K. Gardiner, Elizabeth E. Blood Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels Cell Biology Hematology Immunology Biochemistry |
| author_sort |
al-tamimi, mohammad |
| spelling |
Al-Tamimi, Mohammad Tan, Chee Wee Qiao, Jianlin Pennings, Gabrielle J. Javadzadegan, Ashkan Yong, Andy S. C. Arthur, Jane F. Davis, Amanda K. Jing, Jing Mu, Fi-Tjen Hamilton, Justin R. Jackson, Shaun P. Ludwig, Andreas Berndt, Michael C. Ward, Christopher M. Kritharides, Leonard Andrews, Robert K. Gardiner, Elizabeth E. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2011-10-386607 <jats:title>Abstract</jats:title> <jats:p>Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds−1) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of αIIbβ3, GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds−1 (peak shear, 19 224 seconds−1). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.</jats:p> Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels Blood |
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| title |
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_unstemmed |
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_full |
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_fullStr |
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_full_unstemmed |
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_short |
Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_sort |
pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein vi in stenosed coronary vessels |
| topic |
Cell Biology Hematology Immunology Biochemistry |
| url |
http://dx.doi.org/10.1182/blood-2011-10-386607 |
| publishDate |
2012 |
| physical |
4311-4320 |
| description |
<jats:title>Abstract</jats:title>
<jats:p>Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds−1) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of αIIbβ3, GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds−1 (peak shear, 19 224 seconds−1). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.</jats:p> |
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| author | Al-Tamimi, Mohammad, Tan, Chee Wee, Qiao, Jianlin, Pennings, Gabrielle J., Javadzadegan, Ashkan, Yong, Andy S. C., Arthur, Jane F., Davis, Amanda K., Jing, Jing, Mu, Fi-Tjen, Hamilton, Justin R., Jackson, Shaun P., Ludwig, Andreas, Berndt, Michael C., Ward, Christopher M., Kritharides, Leonard, Andrews, Robert K., Gardiner, Elizabeth E. |
| author_facet | Al-Tamimi, Mohammad, Tan, Chee Wee, Qiao, Jianlin, Pennings, Gabrielle J., Javadzadegan, Ashkan, Yong, Andy S. C., Arthur, Jane F., Davis, Amanda K., Jing, Jing, Mu, Fi-Tjen, Hamilton, Justin R., Jackson, Shaun P., Ludwig, Andreas, Berndt, Michael C., Ward, Christopher M., Kritharides, Leonard, Andrews, Robert K., Gardiner, Elizabeth E., Al-Tamimi, Mohammad, Tan, Chee Wee, Qiao, Jianlin, Pennings, Gabrielle J., Javadzadegan, Ashkan, Yong, Andy S. C., Arthur, Jane F., Davis, Amanda K., Jing, Jing, Mu, Fi-Tjen, Hamilton, Justin R., Jackson, Shaun P., Ludwig, Andreas, Berndt, Michael C., Ward, Christopher M., Kritharides, Leonard, Andrews, Robert K., Gardiner, Elizabeth E. |
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| description | <jats:title>Abstract</jats:title> <jats:p>Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds−1) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of αIIbβ3, GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds−1 (peak shear, 19 224 seconds−1). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.</jats:p> |
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| imprint_str_mv | American Society of Hematology, 2012 |
| institution | DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14 |
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| spelling | Al-Tamimi, Mohammad Tan, Chee Wee Qiao, Jianlin Pennings, Gabrielle J. Javadzadegan, Ashkan Yong, Andy S. C. Arthur, Jane F. Davis, Amanda K. Jing, Jing Mu, Fi-Tjen Hamilton, Justin R. Jackson, Shaun P. Ludwig, Andreas Berndt, Michael C. Ward, Christopher M. Kritharides, Leonard Andrews, Robert K. Gardiner, Elizabeth E. 0006-4971 1528-0020 American Society of Hematology Cell Biology Hematology Immunology Biochemistry http://dx.doi.org/10.1182/blood-2011-10-386607 <jats:title>Abstract</jats:title> <jats:p>Ligand-induced ectodomain shedding of glycoprotein VI (GPVI) is a metalloproteinase-dependent event. We examined whether shear force, in the absence of GPVI ligand, was sufficient to induce shedding of GPVI. Human-citrated platelet-rich plasma or washed platelets were subjected to increasing shear rates in a cone-plate viscometer, and levels of intact and cleaved GPVI were examined by Western blot and ELISA. Pathophysiologic shear rates (3000-10 000 seconds−1) induced platelet aggregation and metalloproteinase-dependent appearance of soluble GPVI ectodomain, and GPVI platelet remnant. Shedding of GPVI continued after transient exposure to shear. Blockade of αIIbβ3, GPIbα, or intracellular signaling inhibited shear-induced platelet aggregation but minimally affected shear-induced shedding of GPVI. Shear-induced GPVI shedding also occurred in platelet-rich plasma or washed platelets isolated from a von Willebrand disease type 3 patient with no detectable VWF, implying that shear-induced activation of platelet metalloproteinases can occur in the absence of GPVI and GPIbα ligands. Significantly elevated levels of sGPVI were observed in 10 patients with stable angina pectoris, with well-defined single vessel coronary artery disease and mean intracoronary shear estimates at 2935 seconds−1 (peak shear, 19 224 seconds−1). Loss of GPVI in platelets exposed to shear has potential implications for the stability of a forming thrombus at arterial shear rates.</jats:p> Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels Blood |
| spellingShingle | Al-Tamimi, Mohammad, Tan, Chee Wee, Qiao, Jianlin, Pennings, Gabrielle J., Javadzadegan, Ashkan, Yong, Andy S. C., Arthur, Jane F., Davis, Amanda K., Jing, Jing, Mu, Fi-Tjen, Hamilton, Justin R., Jackson, Shaun P., Ludwig, Andreas, Berndt, Michael C., Ward, Christopher M., Kritharides, Leonard, Andrews, Robert K., Gardiner, Elizabeth E., Blood, Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels, Cell Biology, Hematology, Immunology, Biochemistry |
| title | Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_full | Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_fullStr | Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_full_unstemmed | Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_short | Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| title_sort | pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein vi in stenosed coronary vessels |
| title_unstemmed | Pathologic shear triggers shedding of vascular receptors: a novel mechanism for down-regulation of platelet glycoprotein VI in stenosed coronary vessels |
| topic | Cell Biology, Hematology, Immunology, Biochemistry |
| url | http://dx.doi.org/10.1182/blood-2011-10-386607 |