| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
American Journal of Pathology, Vol 147, 1649-1660, Copyright © 1995 by American Society for Investigative Pathology
REGULAR ARTICLES |
S Takeshita, ST Rossow, M Kearney, LP Zheng, C Bauters, S Bunting, N Ferrara, JF Symes and JM Isner
Department of Medicine (Cardiology), St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA.
Proliferation of vascular cells has been previously shown to contribute to spontaneous development of coronary collaterals. Recent studies from several laboratories have established that collateral artery growth in both the heart and limb can be enhanced by administration of angiogenic growth factors, or therapeutic angiogenesis. In this study, we sought (1) to define the extent and time course of endothelial cell (EC) and smooth muscle cell (SMC) proliferation accompanying spontaneous collateral development during limb ischemia and (2) to determine the extent to which proliferative activity of ECs and SMCs is augmented during therapeutic angiogenesis with vascular endothelial growth factor (VEGF), a heparin-binding EC-specific mitogen. Ten days after induction of limb ischemia by surgically excising the femoral artery of rabbits, either VEGF (500 to 1000 micrograms) or saline was administered as a bolus into the iliac artery of the ischemic limb. Cellular proliferation was evaluated by bromodeoxyuridine labeling for 24 hours at day 0 (immediately before VEGF administration) and at days 3, 5, and 7 after VEGF, EC proliferation in the midzone collaterals of VEGF- treated animals increased 2.8-fold at day 5 (P < 0.05 versus control), and returned to baseline levels by day 7. SMC proliferation in midzone collaterals also increased 2.7-fold in response to VEGF (P < 0.05). No significant increase in EC or SMC proliferation was observed in either the stem or re-entry collaterals of VEGF-treated animals compared with untreated ischemic control animals. Reduction of hemodynamic deficit in the ischemic limb measured by lower limb blood pressure was documented at day 7 after VEGF (P < 0.01 versus untreated, ischemic control). These data thus (1) establish the contribution of cellular proliferation to collateral vessel development in limb ischemia and (2) support the concept that augmented cellular proliferation contributes to the enhanced formation of collateral vessels after therapeutic angiogenesis with VEGF.
This article has been cited by other articles:
 |
|
 |
|
  H. Iwasaki, K. Fukushima, A. Kawamoto, K. Umetani, A. Oyamada, S. Hayashi, T. Matsumoto, M. Ishikawa, T. Shibata, H. Nishimura, et al. Synchrotron Radiation Coronary Microangiography for Morphometric and Physiological Evaluation of Myocardial Neovascularization Induced by Endothelial Progenitor Cell Transplantation Arterioscler. Thromb. Vasc. Biol., June 1, 2007; 27(6): 1326 - 1333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Baumgartner, H. C. Thoeny, O. Kummer, C. Roefke, C. Skjelsvik, C. Boesch, and R. Kreis Leg Ischemia: Assessment with MR Angiography and Spectroscopy Radiology, March 1, 2005; 234(3): 833 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Hutter, F. E. Carrick, C. Valdiviezo, C. Wolinsky, J. S. Rudge, S. J. Wiegand, V. Fuster, J. J. Badimon, and B. V. Sauter Vascular Endothelial Growth Factor Regulates Reendothelialization and Neointima Formation in a Mouse Model of Arterial Injury Circulation, October 19, 2004; 110(16): 2430 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kinnaird, E. Stabile, M. S. Burnett, and S. E. Epstein Bone Marrow-Derived Cells for Enhancing Collateral Development: Mechanisms, Animal Data, and Initial Clinical Experiences Circ. Res., August 20, 2004; 95(4): 354 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C Hershey, H. A Corcoran, E. P Baskin, D. B Gilberto, X. Mao, K. A Thomas, and J. J Cook Enhanced hindlimb collateralization induced by acidic fibroblast growth factor is dependent upon femoral artery extraction Cardiovasc Res, October 1, 2003; 59(4): 997 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. R Mohler III, C. M Sehgal, V. A Ferrari, M. Parmacek, A. Shih, and R. L Wilensky A novel ultrasound method for evaluation of collateral development in limb ischemia Vascular Medicine, August 1, 2002; 7(3): 169 - 175. [Abstract] [PDF]
|
|
|
|
 |
|
 R Tabibiazar and S.G Rockson Angiogenesis and the ischaemic heart Eur. Heart J., June 1, 2001; 22(11): 903 - 918. [PDF]
|
|
|
|
 |
|
 Y. Dor, R. Porat, and E. Keshet Vascular endothelial growth factor and vascular adjustments to perturbations in oxygen homeostasis Am J Physiol Cell Physiol, June 1, 2001; 280(6): C1367 - C1374. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Simovic, J. M. Isner, A. H. Ropper, A. Pieczek, and D. H. Weinberg Improvement in Chronic Ischemic Neuropathy After Intramuscular phVEGF165 Gene Transfer in Patients With Critical Limb Ischemia Arch Neurol, May 1, 2001; 58(5): 761 - 768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Simons Therapeutic coronary angiogenesis: a fronte praecipitium a tergo lupi? Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H1923 - H1927. [Full Text] [PDF]
|
|
|
|
|
|
M. J. Post, R. Laham, F. W. Sellke, and M. Simons Therapeutic angiogenesis in cardiology using protein formulations Cardiovasc Res, February 16, 2001; 49(3): 522 - 531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Hershey, E. P. Baskin, J. D. Glass, H. A. Hartman, D. B. Gilberto, I. T. Rogers, and J. J. Cook Revascularization in the rabbit hindlimb: dissociation between capillary sprouting and arteriogenesis Cardiovasc Res, February 16, 2001; 49(3): 618 - 625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kroon, P Koolwijk, B van der Vecht, and V. van Hinsbergh Hypoxia in combination with FGF-2 induces tube formation by human microvascular endothelial cells in a fibrin matrix: involvement of at least two signal transduction pathways J. Cell Sci., January 2, 2001; 114(4): 825 - 833. [Abstract] [PDF]
|
|
|
|
|
|
D. W. Losordo and J. M. Isner Estrogen and Angiogenesis : A Review Arterioscler. Thromb. Vasc. Biol., January 1, 2001; 21(1): 6 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Lee, M. L. Springer, W. E. Blanco-Bose, R. Shaw, P. C. Ursell, and H. M. Blau VEGF Gene Delivery to Myocardium : Deleterious Effects of Unregulated Expression Circulation, August 22, 2000; 102(8): 898 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Zachary, A. Mathur, S. Yla-Herttuala, and J. Martin Vascular Protection : A Novel Nonangiogenic Cardiovascular Role for Vascular Endothelial Growth Factor Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1512 - 1520. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Yang, Y. Feng, L. A. Allen, A. Protter, and R. L. Terjung Efficacy and specificity of bFGF increased collateral flow in experimental peripheral arterial insufficiency Am J Physiol Heart Circ Physiol, June 1, 2000; 278(6): H1966 - H1973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rivard, M. Silver, D. Chen, M. Kearney, M. Magner, B. Annex, K. Peters, and J. M. Isner Rescue of Diabetes-Related Impairment of Angiogenesis by Intramuscular Gene Therapy with Adeno-VEGF Am. J. Pathol., February 1, 1999; 154(2): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rivard, J.-E. Fabre, M. Silver, D. Chen, T. Murohara, M. Kearney, M. Magner, T. Asahara, and J. M. Isner Age-Dependent Impairment of Angiogenesis Circulation, January 12, 1999; 99(1): 111 - 120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ma, J. Y. C. Chow, and C. H. Cho Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach Am J Physiol Gastrointest Liver Physiol, January 1, 1999; 276(1): G238 - G248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Witzenbichler, T. Asahara, T. Murohara, M. Silver, I. Spyridopoulos, M. Magner, N. Principe, M. Kearney, J.-S. Hu, and J. M. Isner Vascular Endothelial Growth Factor-C (VEGF-C/VEGF-2) Promotes Angiogenesis in the Setting of Tissue Ischemia Am. J. Pathol., August 1, 1998; 153(2): 381 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Murohara, J. R. Horowitz, M. Silver, Y. Tsurumi, D. Chen, A. Sullivan, and J. M. Isner Vascular Endothelial Growth Factor/Vascular Permeability Factor Enhances Vascular Permeability Via Nitric Oxide and Prostacyclin Circulation, January 13, 1998; 97(1): 99 - 107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Van Belle, A. Rivard, D. Chen, M. Silver, S. Bunting, N. Ferrara, J. F. Symes, C. Bauters, and J. M. Isner Hypercholesterolemia Attenuates Angiogenesis but Does Not Preclude Augmentation by Angiogenic Cytokines Circulation, October 21, 1997; 96(8): 2667 - 2674. [Abstract] [Full Text]
|
|
|
|
|
|
H. Tabata, M. Silver, and J. M Isner Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA Cardiovasc Res, September 1, 1997; 35(3): 470 - 479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Pepper Manipulating Angiogenesis: From Basic Science to the Bedside Arterioscler. Thromb. Vasc. Biol., April 1, 1997; 17(4): 605 - 619. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Tsurumi, S. Takeshita, D. Chen, M. Kearney, S. T. Rossow, J. Passeri, J. R. Horowitz, J. F. Symes, and J. M. Isner Direct Intramuscular Gene Transfer of Naked DNA Encoding Vascular Endothelial Growth Factor Augments Collateral Development and Tissue Perfusion Circulation, December 15, 1996; 94(12): 3281 - 3290. [Abstract] [Full Text]
|
|
|
|
|
|
V. Lindner and M. A. Reidy Expression of VEGF Receptors in Arteries After Endothelial Injury and Lack of Increased Endothelial Regrowth in Response to VEGF Arterioscler. Thromb. Vasc. Biol., November 1, 1996; 16(11): 1399 - 1405. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
