Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow

Birgit Assmus, Masayoshi Iwasaki, Volker Schächinger, Tino Roexe, Masamichi Koyanagi, Kazuma Iekushi, Quanfu Xu, Torsten Tonn, Erhard Seifried, Stefan Liebner, Wolfgang Tilman Kranert, Frank Grünwald, Stefanie Dimmeler, Andreas M. Zeiher

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47 Citations (Scopus)

Abstract

Aims We aimed to characterize the influence of acute myocardial infarction (AMI) on the metabolic activity of the bone marrow (BM) and on the composition and functional activity of BM-derived mononuclear cells (BMC). Acute ischaemia or other stressors induce the mobilization of progenitor cells from the BM stem cell niche. The effect of AMI on the numbers and functional activity of cells within the BM is unknown. Methods and resultsIn patients of the REPAIR-AMI trial as well as in mice, the number and functionality of BMC was compared with respect to the time interval from AMI. Activation of Wnt signalling was assessed after AMI induction in TOP-GAL transgenic reporter mice, carrying a β-galactosidase gene driven by an LEF/TCF/β-catenin responsive promoter. The metabolic activity of the BM, as determined by F-18-fluorodeoxyglucose-positron emission tomography, was significantly higher in patients with AMI compared with patients with chronic post-ischaemic heart failure. Moreover, the number of haematopoietic CD34 (P < 0.05) and CD133 (P < 0.05) cells in the BM aspirates was significantly increased in patients within 7 days after AMI. In order to confirm these clinical data, we induced AMI in mice, which time-dependently increased the number of c-kit Sca-1 lin- cells and colony-forming units in the BM. Activation of the BM by AMI induced a significant increase in Wnt signalling, which is known to induce proliferation of haematopoietic stem cells, and demonstrated increased levels of the Wnt target Axin-2 in BM-derived cells on Day 7 (P < 0.01 vs. control). ConclusionAcute myocardial infarction is associated with an increased metabolic activity and increased levels of progenitor cells within days after AMI. These findings document an activation of the stem cell niche within the BM following AMI, which may have important implications for the optimal timing of cell aspirations used for therapeutic application in patients with AMI.

Original languageEnglish
Pages (from-to)1911-1919
Number of pages9
JournalEuropean heart journal
Volume33
Issue number15
DOIs
Publication statusPublished - Aug 1 2012

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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    Assmus, B., Iwasaki, M., Schächinger, V., Roexe, T., Koyanagi, M., Iekushi, K., Xu, Q., Tonn, T., Seifried, E., Liebner, S., Kranert, W. T., Grünwald, F., Dimmeler, S., & Zeiher, A. M. (2012). Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow. European heart journal, 33(15), 1911-1919. https://doi.org/10.1093/eurheartj/ehr388