title: Cardiac pressure overload initiates a systemic stem cell response.
abstract: OBJECTIVE
  Acute cardiac injury results in the activation and recruitment of resident and non-cardiac stem cells. In this study we sought to define the pattern of peripheral stem cells and resident cardiac stem cell (CSC) activation induced acutely by cardiac pressure overload (PO).
  
  
  METHODS
  PO was induced in mice by transaortic constriction (TAC). CSC, endothelial progenitor cells (EPC), hematopoietic stem cells (HSC) and stage-specific embryonic antigen (SSEA)-1(+) cells were profiled in the heart, spleen and bone marrow after TAC by flow cytometry.
  
  
  RESULTS
  The combination of a systemic and local stem cell response resulted in increases in SSEA-1 (+) cells and EPC in the heart 7 and 14 days post-TAC, respectively. Locally, modest SSEA-1(+) proliferation at 4 days preceded the elevated myocardial stem cell number. We observed no significant proliferation of EPC and CSC in the heart. The systemic stem cell response was characterized by a biphasic loss of splenic SSEA-1(+) cells at 2 and 7 days post-TAC and loss of bone marrow and spleen EPC at 4 and 7 days, respectively. Spleen size changed dynamically after TAC. A negligible response of HSC to TAC was observed. Significant EPC and SSEA-1(+) proliferation in the bone marrow and spleen occurred only after their local levels were decreased.
  
  
  CONCLUSIONS
  Our results demonstrate that an orchestrated systemic stem cell response (EPC and SSEA-1 (+) ) takes place in response to TAC. The increase of SSEA-1(+) cells and EPC in the heart in response to pressure is likely to be because of a combination of local proliferation and stem cell recruitment.
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Finan
authors.forename: Matthew
authors.initials: M
authors.lastname: Kiedrowski
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Turturice
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Sopko
authors.forename: Marc S
authors.initials: MS
authors.lastname: Penn
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006335:Heart Injuries; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism; D016256:Lewis X Antigen / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D011312:Pressure; D013154:Spleen / Q000378:metabolism
chemical_list: D016256:Lewis X Antigen