title: Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  In 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).
  
  
  CONCLUSIONS
  Acute 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.
authors.affiliation: Division of Cardiology, Department of Medicine III, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt,  Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Assmus
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Volker
authors.initials: V
authors.lastname: Schächinger
authors.forename: Tino
authors.initials: T
authors.lastname: Roexe
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Kazuma
authors.initials: K
authors.lastname: Iekushi
authors.forename: Quanfu
authors.initials: Q
authors.lastname: Xu
authors.forename: Torsten
authors.initials: T
authors.lastname: Tonn
authors.forename: Erhard
authors.initials: E
authors.lastname: Seifried
authors.forename: Stefan
authors.initials: S
authors.lastname: Liebner
authors.forename: Wolfgang Tilman
authors.initials: WT
authors.lastname: Kranert
authors.forename: Frank
authors.initials: F
authors.lastname: Grünwald
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D049109:Cell Proliferation; D054377:Chemokine CXCL12 / Q000494:pharmacology; D002630:Chemotactic Factors / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D019275:Radiopharmaceuticals; D016032:Randomized Controlled Trials as Topic; D015398:Signal Transduction / Q000502:physiology*; D051155:Wnt1 Protein / Q000378:metabolism*; D060509:Wnt3A Protein / Q000494:pharmacology
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D002630:Chemotactic Factors; D019275:Radiopharmaceuticals; C555510:WNT3A protein, human; D051155:Wnt1 Protein; D060509:Wnt3A Protein; D019788:Fluorodeoxyglucose F18