High-resolution quantitative computed tomography demonstrating selective enhancement of medium-size collaterals by placental growth factor-1 in the mouse ischemic hindlimb

• Published in: Circulation (New York, N.Y.) N.Y.), 2006-05, Vol.113 (20), p.2445-2453
• Main Authors: WEIMING LI, WEIQUN SHEN, GUOMING WANG, WAGLE, Asavari, HUI, Kwan, WESTMORE, Michael, HANSON, Jeffrey, CHEN, Yun-Fei, SIMONS, Michael, SINGH, Jaipal, GILL, Robert, CORBLY, Angela, JONES, Bonita, BELAGAJE, Rama, YUKE ZHANG, SHAOQING TANG, YAN CHEN, YAN ZHAI
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biological Assay; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Cloning, Molecular; Collateral Circulation - drug effects; Disease Models, Animal; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Fundamental and applied biological sciences. Psychology; Hindlimb - blood supply; Hormones. Endocrine system; Ischemia - drug therapy; Male; Medical sciences; Membrane Proteins; Mice; Mice, Inbred BALB C; Pharmacology. Drug treatments; Proteins - genetics; Proteins - therapeutic use; Restriction Mapping; Tomography, X-Ray Computed; Vertebrates: cardiovascular system
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/circulationaha.105.586818

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. 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. 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.