Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients
Article first published online: 12 APR 2013
© 2013 The Authors Journal of Cellular and Molecular Medicine Published by Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
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Journal of Cellular and Molecular Medicine
Volume 17, Issue 5, pages 636–647, May 2013
How to Cite
López, E., Berna-Erro, A., Bermejo, N., Brull, J. M., Martinez, R., Garcia Pino, G., Alvarado, R., Salido, G. M., Rosado, J. A., Cubero, J. J. and Redondo, P. C. (2013), Long-term mTOR inhibitors administration evokes altered calcium homeostasis and platelet dysfunction in kidney transplant patients. Journal of Cellular and Molecular Medicine, 17: 636–647. doi: 10.1111/jcmm.12044
- Issue published online: 27 MAY 2013
- Article first published online: 12 APR 2013
- Manuscript Accepted: 31 JAN 2013
- Manuscript Received: 16 JUL 2012
- MEC. Grant Number: BFU2010-21043-C02-01
- Junta de Extremadura-FEDER. Grant Numbers: GR10010, PRIBS10020
- mTOR ;
The use of the mammal target of rapamycin (mTOR) inhibitors has been consolidated as the therapy of election for preventing graft rejection in kidney transplant patients, despite their immunosuppressive activity is less strong than anti-calcineurin agents like tacrolimus and cyclosporine A. Furthermore, as mTOR is widely expressed, rapamycin (a macrolide antibiotic produced by Streptomyces hygroscopicus) is recommended in patients presenting neoplasia due to its antiproliferative actions. Hence, we have investigated whether rapamycin presents side effects in the physiology of other cell types different from leucocytes, such as platelets. Blood samples were drawn from healthy volunteers and kidney transplant patients long-term medicated with rapamycin: sirolimus and everolimus. Platelets were either loaded with fura-2 or directly stimulated, and immunoassayed or fixed with Laemmli's buffer to perform the subsequent analysis of platelet physiology. Our results indicate that rapamycin evokes a biphasic time-dependent alteration in calcium homeostasis and function in platelets from kidney transplant patients under rapamycin regime, as demonstrated by the reduction in granule secretion observed and subsequent impairment of platelet aggregation in these patients compared with healthy volunteers. Platelet count was also reduced in these patients, thus 41% of patients presented thrombocytopenia. All together our results show that long-term administration of rapamycin to kidney transplant patients evokes alteration in platelet function.