Evidence suggests that PTHrP [PTH (parathyroid hormone)-related protein] can act as an inflammatory mediator in several pathological settings including cardiovascular disease. The aim of the present study was to determine whether PTHrP might be involved in human platelet activation. We used a turbidimetric method to determine platelet aggregation. The expression of PTH1R (PTH type 1 receptor) in human platelets was analysed by Western blot and flow cytometry analyses. PTHrP-(1–36) (10−7 mol/l) by itself failed to modify the activation of platelets. However, it significantly enhanced ADP-induced platelet activation, and also increased the ability of other agonists (thrombin, collagen and arachidonic acid) to induce platelet aggregation. H89 (10−6 mol/l) and 25×10−6 mol/l Rp-cAMPS (adenosine 3′,5′-cyclic monophosphorothioate Rp-isomer), two protein kinase A inhibitors, and 25×10−9 mol/l bisindolylmaleimide I, a protein kinase C inhibitor, partially decreased the enhancing effect of PTHrP-(1–36) on ADP-induced platelet activation. Meanwhile, 10−6 mol/l PTHrP-(7–34), a PTH1R antagonist, as well as 10−5 mol/l PD098059, a MAPK (mitogen-activated protein kinase) inhibitor, or a farnesyltransferase inhibitor abolished this effect of PTHrP-(1–36). Moreover, 10−7 mol/l PTHrP-(1–36) increased (2-fold over control) MAPK activation in human platelets. PTH1R was detected in platelets, and the number of platelets expressing it on their surface in patients during AMI (acute myocardial infarction) was not different from that in a group of patients with similar cardiovascular risk factors without AMI. Western blot analysis showed that total PTH1R protein levels were markedly higher in platelets from control than those from AMI patients. PTH1R was found in plasma, where its levels were increased in AMI patients compared with controls. In conclusion, human platelets express the PTH1R. PTHrP can interact with this receptor to enhance human platelet activation induced by several agonists through a MAPK-dependent mechanism.
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October 2007
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Research Article|
September 03 2007
Effect of parathyroid-hormone-related protein on human platelet activation
Arantxa Ortega;
Arantxa Ortega
1
*Bone and Mineral Metabolism Laboratory, Fundación Jiménez Díaz, 28040 Madrid, Spain
∥Physiology Department, University of Alcalá, Alcalá de Henares, 28801 Madrid, Spain
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Ma Teresa Pérez de Prada;
Ma Teresa Pérez de Prada
1
†Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Petra J. Mateos-Cáceres;
Petra J. Mateos-Cáceres
†Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Priscila Ramos Mozo;
Priscila Ramos Mozo
†Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Juan J. González-Armengol;
Juan J. González-Armengol
‡Emergency Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Juan M. González del Castillo;
Juan M. González del Castillo
‡Emergency Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Javier Martín Sánchez;
Javier Martín Sánchez
‡Emergency Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Pedro Villarroel;
Pedro Villarroel
‡Emergency Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
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José L. Santiago;
José L. Santiago
§Immunology Department, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Ricardo J. Bosch;
Ricardo J. Bosch
∥Physiology Department, University of Alcalá, Alcalá de Henares, 28801 Madrid, Spain
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Carlos Macaya;
Carlos Macaya
†Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, 28040 Madrid, Spain
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Pedro Esbrit;
Pedro Esbrit
2
*Bone and Mineral Metabolism Laboratory, Fundación Jiménez Díaz, 28040 Madrid, Spain
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Antonio J. López-Farré
Antonio J. López-Farré
2
†Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clínico San Carlos, 28040 Madrid, Spain
Correspondence: Dr Antonio J. López-Farré (email [email protected]).
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Publisher: Portland Press Ltd
Received:
January 05 2007
Revision Received:
May 09 2007
Accepted:
May 14 2007
Accepted Manuscript online:
May 14 2007
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2007 Biochemical Society
2007
Clin Sci (Lond) (2007) 113 (7): 319–327.
Article history
Received:
January 05 2007
Revision Received:
May 09 2007
Accepted:
May 14 2007
Accepted Manuscript online:
May 14 2007
Citation
Arantxa Ortega, Ma Teresa Pérez de Prada, Petra J. Mateos-Cáceres, Priscila Ramos Mozo, Juan J. González-Armengol, Juan M. González del Castillo, Javier Martín Sánchez, Pedro Villarroel, José L. Santiago, Ricardo J. Bosch, Carlos Macaya, Pedro Esbrit, Antonio J. López-Farré; Effect of parathyroid-hormone-related protein on human platelet activation. Clin Sci (Lond) 1 October 2007; 113 (7): 319–327. doi: https://doi.org/10.1042/CS20070010
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