title: B-type natriuretic peptide enhances vasculogenesis by promoting number and functional properties of early endothelial progenitor cells.
abstract: OBJECTIVE
  To test the hypothesis that B-type natriuretic peptide (BNP) acts as a potent vasculogenic agent by enhancing the number, proliferation, adhesion, and migration of endothelial progenitor cells (EPCs).
  
  
  BACKGROUND
  BNP is a neurohormonal peptide that predicts outcome and used for treatment in chronic heart failure patients. It has been shown to promote angiogenesis in experimental animals. EPCs have been demonstrated to contribute to postnatal angiogenesis and vasculogenesis.
  
  
  METHODS
  The number of EPC colony forming units (CFU) and levels of N-terminal ProBNP were assayed in patients with severe, yet controlled, New York Heart Association (NYHA) II-IV heart failure. The in vitro effects of BNP on early EPC-CFU numbers, proliferation, migration, adhesive, and vascular tube formation capacities were studied using human and murine systems. The effects of in vivo BNP administration on Sca-1/Flk-1 progenitors and on vasculogenesis in the hindlimb ischemia model were then assayed in wild-type mice.
  
  
  RESULTS
  A significant correlation was found between circulating N-terminal ProBNP levels and EPC-CFU numbers. We observed a dose-dependent effect of BNP on the numbers of CFU and proliferation capacity of human EPCs as well as on their adhesive, migratory, and tube formation properties, in vitro. Systemic BNP administration to mice led to a significant increase in bone marrow Sca-1/Flk-1 EPCs and improvement in blood flow and capillary density in the ischemic limbs of mice.
  
  
  CONCLUSIONS
  BNP promotes vessel growth by increasing the number of endothelial progenitors and enhancing their functional properties. These provasculogenic properties of BNP could account for some of its beneficial effects in chronic heart failure patients and may be harnessed for the purpose of improving collateral formation in ischemic subjects.
authors.affiliation: Department of Cardiology, Tel Aviv Sourasky Medical Center, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Shmilovich
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ben-Shoshan
authors.forename: Reshef
authors.initials: R
authors.lastname: Tal
authors.forename: Arnon
authors.initials: A
authors.lastname: Afek
authors.forename: Iris
authors.initials: I
authors.lastname: Barshack
authors.forename: Sofia
authors.initials: S
authors.lastname: Maysel-Auslander
authors.forename: Dror
authors.initials: D
authors.lastname: Harats
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
authors.forename: Jacob
authors.initials: J
authors.lastname: George
mesh_terms: D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006333:Heart Failure / Q000097:blood; D006801:Humans; D007511:Ischemia; D007797:Laminin / Q000378:metabolism; D051379:Mice; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D009389:Neovascularization, Pathologic / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: C000593749:ATXN1 protein, human; D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D004338:Drug Combinations; D007797:Laminin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011509:Proteoglycans; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; C059485:matrigel; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1