title: The cardioprotective effects of parathyroid hormone are independent of endogenous granulocyte-colony stimulating factor release.
abstract: OBJECTIVE
  Parathyroid hormone (PTH) administration after myocardial infarction (MI) is known to attenuate ischaemic cardiomyopathy. This effect mainly resulted from an increase in mobilization and homing of CD34+/CD45+ cells into the ischaemic myocardium. PTH-related stem cell mobilization was shown to be related to endogenous granulocyte-colony stimulating factor (G-CSF) release. The aim of our study is to determine the role of G-CSF on the cardioprotective effects of PTH.
  
  
  RESULTS
  G-CSF +/+ (C57BL/6) and G-CSF -/- mice were treated with PTH for 6 days after inducing a MI. The myocardial homing factor stromal cell-derived factor-1 (SDF-1) was analysed on day 2 with enzyme-linked immunosorbent assay. Stem cell populations in peripheral blood and hearts were examined by FACS on days 6 and 2, respectively. Cardiac function and immunohistochemistry were investigated on day 6 and day 30. PTH treatment resulted in a significant increase in CD45+/CD34+ cells in peripheral blood in G-CSF +/+ but not in G-CSF -/- mice. However, a significant increase in SDF-1 and enhanced migration of CD45+/CD34+ cells into the ischaemic myocardium was revealed after PTH administration in both G-CSF +/+ and G-CSF -/- mice. Enhanced stem cell homing was associated with improved cardiac function and post-MI survival after PTH treatment. Furthermore, infarct size, wall thickness, and neovascularization showed a significant improvement in both groups 30 days after MI.
  
  
  CONCLUSIONS
  The cardioprotective effects of PTH were shown to be independent of endogenous G-CSF release and therefore from stem cell mobilization. This puts more emphasis on the role of stem cell homing into ischaemic myocardium.
authors.affiliation: Department of Internal Medicine I,  Ludwig-Maximilians-University, Campus Grosshadern, Munich,  Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Tobias
authors.initials: T
authors.lastname: Weinberger
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Huber
authors.forename: Alexander
authors.initials: A
authors.lastname: Segeth
authors.forename: Marc-Michael
authors.initials: MM
authors.lastname: Zaruba
authors.forename: Hans D
authors.initials: HD
authors.lastname: Theiss
authors.forename: Gerald
authors.initials: G
authors.lastname: Assmann
authors.forename: Nadja
authors.initials: N
authors.lastname: Herbach
authors.forename: Ruediger
authors.initials: R
authors.lastname: Wanke
authors.forename: Josef
authors.initials: J
authors.lastname: Mueller-Hoecker
authors.forename: Wolfgang-Michael
authors.initials: WM
authors.lastname: Franz
mesh_terms: D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006321:Heart / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017202:Myocardial Ischemia / Q000473:pathology; D010281:Parathyroid Hormone / Q000494:pharmacology*
chemical_list: D010281:Parathyroid Hormone; D016179:Granulocyte Colony-Stimulating Factor