title: Biochemically engineered stromal cell-derived factor 1-alpha analog increases perfusion in the ischemic hind limb.
abstract: Despite promising therapeutic innovation over the last decade, peripheral arterial disease remains a prevalent morbidity, as many patients are still challenged with peripheral ischemia. We hypothesized that delivery of engineered stromal cell-derived factor 1-alpha (ESA) in an ischemic hind limb will yield significant improvement in perfusion.
  
  
  
  Male rats underwent right femoral artery ligation, and animals were randomized to receive a 100 μL injection of saline (n = 9) or 6 μg/kg dosage of equal volume of ESA (n = 12) into the ipsilateral quadriceps muscle. Both groups of animals were also given an intraperitoneal injection of 40 μg/kg of granulocyte macrophage colony-stimulating factor (GMCSF). Perfusion was quantified using a laser Doppler imaging device preoperatively, and on postoperative days 0, 7, and 14. Immunohistochemistry was performed to quantify angiogenesis on day 14, and an mRNA profile was evaluated for angiogenic and inflammatory markers.
  
  
  
  Compared with the saline/GMCSF group at day 14, the ESA/GMCSF-injected animals had greater reperfusion ratios (Saline/GMCSF, 0.600 ± 0.140 vs ESA/GMCSF, 0.900 ± 0.181; group effect P = .006; time effect P < .0001; group×time effect P < .0001), elevated capillary density (10×; Saline/GMCSF, 6.40 ± 2.01 vs ESA/GMCSF, 18.55 ± 5.30; P < .01), and increased mRNA levels of vascular endothelial growth factor-A (Saline/GMCSF [n = 6], 0.298 ± 0.205 vs ESA/GMCSF [n = 8], 0.456 ± 0.139; P = .03).
  
  
  
  Delivery of ESA significantly improves perfusion in a rat model of peripheral arterial disease via improved neovasculogenesis, a finding which may prove beneficial in the treatment strategy for this debilitating disease.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Edwards
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Fairman
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif; Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Cohen
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif; Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: John W
authors.initials: JW
authors.lastname: MacArthur
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif; Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Goldstone
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Woo
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pa.
authors.forename: William
authors.initials: W
authors.lastname: Hiesinger
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, Calif. Electronic address: joswoo@stanford.edu.
authors.forename: Y Joseph
authors.initials: YJ
authors.lastname: Woo
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001783:Blood Flow Velocity; D054377:Chemokine CXCL12 / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006614:Hindlimb; D018836:Inflammation Mediators / Q000378:metabolism; D007273:Injections, Intramuscular; D007511:Ischemia / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015202:Protein Engineering; D052097:Quadriceps Muscle / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology*; D020127:Recovery of Function; D012039:Regional Blood Flow; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D054377:Chemokine CXCL12; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016178:Granulocyte-Macrophage Colony-Stimulating Factor