title: High-resolution quantitative computed tomography demonstrating selective enhancement of medium-size collaterals by placental growth factor-1 in the mouse ischemic hindlimb.
abstract: BACKGROUND
  The process of arteriogenesis after occlusion of a major artery is poorly understood. We have used high-resolution microcomputed tomography (mu-CT) imaging to define the arteriogenic response in the mouse model of hindlimb ischemia and to examine the effect of placental growth factor-1 (PlGF-1) on this process.
  
  
  RESULTS
  After common femoral artery ligation, mu-CT imaging demonstrated formation of collateral vessels originating near the ligation site in the upper limb and connecting to the ischemic calf muscle region. Three-dimensional mu-CT and quantitative image analysis revealed changes in the number of segments and the segmental volume of vessels, ranging from 8 to 160 microm in diameter. The medium-size vessels (48 to 160 microm) comprising 85% of the vascular volume were the major contributor (188%) to the change in vascular volume in response to ischemia. Intramuscular injections of Ad-PlGF-1 significantly increased Sca1+ cells in the circulation, alpha-actin-stained vessels, and perfusion of the ischemic hindlimb. These effects were predominantly associated with an increase in vascular volume contributed by the medium-size (96 to 144 microm) vessels as determined by mu-CT.
  
  
  CONCLUSIONS
  High-resolution mu-CT delineated the formation of medium-size collaterals representing a major vascular change that contributed to the restoration of vascular volume after ischemia. This effect is selectively potentiated by PlGF-1. Such selective enhancement of arteriogenesis by therapeutically administered PlGF-1 demonstrates a desirable biological activity for promoting the growth of functionally relevant vasculature.
authors.affiliation: Eli Lilly and Co, Indianapolis, IN 46285, USA.
authors.forename: Weiming
authors.initials: W
authors.lastname: Li
authors.forename: Weiqun
authors.initials: W
authors.lastname: Shen
authors.forename: Robert
authors.initials: R
authors.lastname: Gill
authors.forename: Angela
authors.initials: A
authors.lastname: Corbly
authors.forename: Bonita
authors.initials: B
authors.lastname: Jones
authors.forename: Rama
authors.initials: R
authors.lastname: Belagaje
authors.forename: Yuke
authors.initials: Y
authors.lastname: Zhang
authors.forename: Shaoqing
authors.initials: S
authors.lastname: Tang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhai
authors.forename: Guoming
authors.initials: G
authors.lastname: Wang
authors.forename: Asavari
authors.initials: A
authors.lastname: Wagle
authors.forename: Kwan
authors.initials: K
authors.lastname: Hui
authors.forename: Michael
authors.initials: M
authors.lastname: Westmore
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Hanson
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Simons
authors.forename: JaiPal
authors.initials: J
authors.lastname: Singh
mesh_terms: D000818:Animals; D001681:Biological Assay; D003001:Cloning, Molecular; D003097:Collateral Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000188:drug therapy*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D011506:Proteins / Q000235:genetics / Q000627:therapeutic use*; D015183:Restriction Mapping; D014057:Tomography, X-Ray Computed
chemical_list: D008565:Membrane Proteins; C098069:PIGF protein, human; D011506:Proteins