High-resolution quantitative computed tomography demonstrating selective enhancement of medium-size collaterals by placental growth factor-1 in the mouse ischemic hindlimb.
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.
Li
Weiming
W
Eli Lilly and Co, Indianapolis, IN 46285, USA.
Shen
Weiqun
W
Gill
Robert
R
Corbly
Angela
A
Jones
Bonita
B
Belagaje
Rama
R
Zhang
Yuke
Y
Tang
Shaoqing
S
Chen
Yan
Y
Zhai
Yan
Y
Wang
Guoming
G
Wagle
Asavari
A
Hui
Kwan
K
Westmore
Michael
M
Hanson
Jeffrey
J
Chen
Yun-Fei
YF
Simons
Michael
M
Singh
JaiPal
J
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
D008565:Membrane Proteins; C098069:PIGF protein, human; D011506:Proteins