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Blood, 15 August 2004, Vol. 104, No. 4, pp. 978-985. Prepublished online as a Blood First Edition Paper on April 22, 2004; DOI 10.1182/blood-2003-11-3828. This Article Full Text (PDF) All Versions of this Article: 2003-11-3828v1 104/4/978    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Charrier, S. Articles by Vainchenker, W. Search for Related Content PubMed PubMed Citation Articles by Charrier, S. Articles by Vainchenker, W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 13, 2003 Accepted March 22, 2004 Inhibition of Angiotensin I-converting enzyme induces radioprotection by preserving murine hematopoietic short-term reconstituting cells Sabine Charrier, Annie Michaud, Sabrina Badaoui, Sebastien Giroux, Eric Ezan, Francoise Sainteny, Pierre Corvol, and William Vainchenker* INSERM U362, Hematopoiese et Cellules Souches, Institut Gustave Roussy, Villejuif, France INSERM U36, Pathologie Vasculaire et Endocrinologie Renale, College-de-France, Paris, France CEA de Saclay, Gif-sur-Yvette, France * Corresponding author; email: verpre{at}igr.fr. Angiotensin I converting enzyme (ACE) inhibitors can affect hematopoiesis by several mechanisms including inhibition of angiotensin II formation and increasing plasma concentrations of AcSDKP, an ACE substrate and a negative regulator of hematopoiesis. We tested whether ACE inhibition could decrease the hematopoietic toxicity of lethal or sublethal irradiation protocols. In all cases, short treatment with the ACE inhibitor perindopril, protected against the irradiation-induced death. ACE inhibition accelerated hematopoietic recovery and led to a significant increase in platelet and red cell counts. Pre-treatment with perindopril increased bone marrow cellularity and the number of hematopoietic progenitors (CFU-GM, BFU-E and CFU-MK) from day 7 to 28 after irradiation. Perindopril also increased the number of hematopoietic stem cells with at least a short-term reconstitutive activity in animals that recovered from irradiation. To determine the mechanism of action involved, we evaluated the effects of increasing AcSDKP plasma concentrations and of an angiotensin II type 1 (AT1) receptor antagonist (Telmisartan) on radioprotection. We found that the AT1-receptor antagonism mediated similar radioprotection as the ACE inhibitor. These results suggest that ACE inhibitors and AT1 receptor antagonists could be used to decrease the hematopoietic toxicity of irradiation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. T. Zambidis, T. Soon Park, W. Yu, A. Tam, M. Levine, X. Yuan, M. Pryzhkova, and B. Peault Expression of angiotensin-converting enzyme (CD143) identifies and regulates primitive hemangioblasts derived from human pluripotent stem cells Blood, November 1, 2008; 112(9): 3601 - 3614. [Abstract] [Full Text] [PDF] T. Thum, D. Fraccarollo, P. Galuppo, D. Tsikas, S. Frantz, G. Ertl, and J. Bauersachs Bone marrow molecular alterations after myocardial infarction: Impact on endothelial progenitor cells Cardiovasc Res, April 1, 2006; 70(1): 50 - 60. [Abstract] [Full Text] [PDF] R. S Richmond, E A. Tallant, P. E Gallagher, C. M Ferrario, and W. B Strawn Angiotensin II stimulates arachidonic acid release from bone marrow stromal cells Journal of Renin-Angiotensin-Aldosterone System, December 1, 2004; 5(4): 176 - 182. [Abstract] [PDF]

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