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European Heart Journal Advance Access originally published online on December 20, 2007
European Heart Journal 2008 29(2):241-250; doi:10.1093/eurheartj/ehm542
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2007. For permissions please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org.

Enhanced functional response of CD133+ circulating progenitor cells in patients early after acute myocardial infarction

Stefan Vöö1, Juliane Eggermann2, Marina Dunaeva1, Carolien Ramakers-van Oosterhoud1 and Johannes Waltenberger1,*

1 Department of Cardiology, University Hospital of Maastricht, P. Debyelaan 25, PO Box 5800, 6202AZ Maastricht, The Netherlands
2 Department of Internal Medicine II, Ulm University Medical Center, Ulm, Germany

Received 11 March 2007; revised 22 October 2007; accepted 25 October 2007; online publish-ahead-of-print 20 December 2007.

* Corresponding author. Tel: +31 43 387 5106, Fax: +31 43 387 5104. Email: j.waltenberger{at}cardio.azm.nl

Aims: Circulating progenitor cells (PC) may contribute to myocardial recovery following infarction. Growth factors including VEGF are produced during ischaemia and stimulate PC release and activation. In this study, we focused on the functional chemotactic response of PC to VEGF in subjects early after myocardial ischaemia.

Methods and results: Number and phenotype of PC were characterized using flow-cytometry. CD133+PC were isolated from peripheral blood using positive MACS isolation. The chemotactic response towards members of the VEGF family (VEGF-A, PlGF-1, and VEGF-E) was analysed in three groups: (i) early period following acute myocardial infarction (days 2–4) treated with primary PCI (AMI) (n = 35), (ii) stable coronary artery disease (CAD) (n = 35), and (iii) controls (CTR) (n = 20). CD133+PC number was 2-fold higher in AMI when compared with CAD and CTR (P = 0.0001), whereas CAD was not different from CTR. The chemotactic response of CD133+PC to VEGF-A, PlGF-1, and VEGF-E was significantly enhanced (2-fold) in AMI when compared with CAD (P = 0.0001). While the increase of the VEGFR-1-mediated/PlGF-triggered response was rapid (2 days following infarction), the VEGFR-2-mediated/VEGF-E-triggered response was maximally increased on day 4 post-AMI, thus correlating with the kinetics of maximal inflammatory activation reflected by increased CRP levels (P = 0.019).

Conclusion: The enhanced chemotactic response of CD133+PC following myocardial infarction represents a novel principle potentially involved in cardiovascular repair early after myocardial infarction. Acute inflammatory processes are closely associated with this increased cellular function.

Key Words: Progenitor cells • CD133 • Myocardial infarction • Inflammation


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