title: Notch1 in bone marrow-derived cells mediates cardiac repair after myocardial infarction.
abstract: BACKGROUND
  The signaling mechanisms that regulate the recruitment of bone marrow (BM)-derived cells to the injured heart are not well known. Notch receptors mediate binary cell fate determination and may regulate the function of BM-derived cells. However, it is not known whether Notch1 signaling in BM-derived cells mediates cardiac repair after myocardial injury.
  
  
  RESULTS
  Mice with postnatal cardiac-specific deletion of Notch1 exhibit infarct size and heart function after ischemic injury that is similar to that of control mice. However, mice with global hemizygous deletion of Notch1 (N1(±)) developed larger infarct size and worsening heart function. When the BM of N1(±) mice were transplanted into wild-type (WT) mice, infarct size and heart function were worsened and neovascularization in the infarct border area was reduced compared with WT mice transplanted with WT BM. In contrast, transplantation of WT BM into N1(±) mice lessened the myocardial injury observed in N1(±) mice. Indeed, hemizygous deletion of Notch1 in BM-derived cells leads to decreased recruitment, proliferation, and survival of mesenchymal stem cells (MSC). Compared with WT MSC, injection of N1(±) MSC into the infarcted heart leads to increased myocardial injury whereas injection of MSC overexpressing Notch intracellular domain leads to decreased infarct size and improved cardiac function.
  
  
  CONCLUSIONS
  These findings indicate that Notch1 signaling in BM-derived cells is critical for cardiac repair and suggest that strategies that increase Notch1 signaling in BM-derived MSC could have therapeutic benefits in patients with ischemic heart disease.
authors.affiliation: Brigham and Women's Hospital, Cambridge, MA 02139, USA.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Li
authors.forename: Yukio
authors.initials: Y
authors.lastname: Hiroi
authors.forename: Soeun
authors.initials: S
authors.lastname: Ngoy
authors.forename: Ryuji
authors.initials: R
authors.lastname: Okamoto
authors.forename: Kensuke
authors.initials: K
authors.lastname: Noma
authors.forename: Chao-Yung
authors.initials: CY
authors.lastname: Wang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhou
authors.forename: Freddy
authors.initials: F
authors.lastname: Radtke
authors.forename: Ronglih
authors.initials: R
authors.lastname: Liao
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D049109:Cell Proliferation; D002470:Cell Survival; D064987:Cell- and Tissue-Based Therapy; D002478:Cells, Cultured; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D049452:Green Fluorescent Proteins