| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco; 2Regeneron Pharmaceuticals, Tarrytown, New York; 3Department of Medicine, Stanford University School of Medicine, Center for Clinical Sciences Research, Stanford; and 4Department of Research Pharmacology, Pfizer Global Research and Development, San Diego, California
Submitted 9 June 2005 ; accepted in final form 8 September 2005
The vasculature of the embryo requires vascular endothelial growth factor (VEGF) during development, but most adult blood vessels lose VEGF dependence. However, some capillaries in the respiratory tract and selected other organs of adult mice regress after VEGF inhibition. The present study sought to identify the sequence of events and the fate of endothelial cells, pericytes, and vascular basement membrane during capillary regression in mouse tracheas after VEGF signaling was blocked with a VEGF-receptor tyrosine kinase inhibitor AG-013736 or soluble receptor construct (VEGF Trap or soluble adenoviral VEGFR-1). Within 1 day, patency was lost and fibrin accumulated in some tracheal capillaries. Apoptotic endothelial cells marked by activated caspase-3 were present in capillaries without blood flow. VEGF inhibition was accompanied by a 19% decrease in tracheal capillaries over 7 days and 30% over 21 days. During this period, desmin/NG2-immunoreactive pericytes moved away from regressing capillaries onto surviving vessels. Empty sleeves of basement membrane, left behind by regressing endothelial cells, persisted for about 2 wk and served as a scaffold for vascular regrowth after treatment ended. The amount of regrowth was limited by the number of surviving basement membrane sleeves. These findings demonstrate that, after inhibition of VEGF signaling, some normal capillaries regress in a systematic sequence of events initiated by a cessation of blood flow and followed by apoptosis of endothelial cells, migration of pericytes away from regressing vessels, and formation of empty basement membrane sleeves that can facilitate capillary regrowth.
apoptosis; basement membrane; endothelial cells; platelet-derived growth factor; pericytes; trachea; vascular endothelial growth factor
This article has been cited by other articles:
|
|
 |
|
  H. Elmasri, C. Karaaslan, Y. Teper, E. Ghelfi, M. Weng, T. A. Ince, H. Kozakewich, J. Bischoff, and S. Cataltepe Fatty acid binding protein 4 is a target of VEGF and a regulator of cell proliferation in endothelial cells FASEB J, November 1, 2009; 23(11): 3865 - 3873. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Whee Park, H. Wook Kim, J. Hee Lim, K. Dong Yoo, S. Chung, S. Joon Shin, H. Wha Chung, S. Ju Lee, C.-B. Chae, Y.-S. Kim, et al. Vascular Endothelial Growth Factor Inhibition by dRK6 Causes Endothelial Apoptosis, Fibrosis, and Inflammation in the Heart via the Akt/eNOS Axis in db/db Mice Diabetes, November 1, 2009; 58(11): 2666 - 2676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Steeghs, T. J. Rabelink, J. op 't Roodt, E. Batman, F. H. M. Cluitmans, N. I. Weijl, E. de Koning, and H. Gelderblom Reversibility of capillary density after discontinuation of bevacizumab treatment Ann. Onc., October 23, 2009; (2009) mdp417v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Okazaki, A. Ni, P. Baluk, O. A. Ayeni, J. Kearley, A. J. Coyle, A. Humbles, and D. M. McDonald Capillary Defects and Exaggerated Inflammatory Response in the Airways of EphA2-Deficient Mice Am. J. Pathol., June 1, 2009; 174(6): 2388 - 2399. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Levy Blood pressure as a potential biomarker of the efficacy angiogenesis inhibitor Ann. Onc., February 1, 2009; 20(2): 200 - 203. [Full Text] [PDF]
|
|
|
|
 |
|
 M. Saint-Geniez, T. Kurihara, and P. A. D'Amore Role of Cell and Matrix-Bound VEGF Isoforms in Lens Development Invest. Ophthalmol. Vis. Sci., January 1, 2009; 50(1): 311 - 321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Patyna, C. Arrigoni, A. Terron, T.-W. Kim, J. K. Heward, S. L. Vonderfecht, R. Denlinger, S. E. Turnquist, and W. Evering Nonclinical Safety Evaluation of Sunitinib: A Potent Inhibitor of VEGF, PDGF, KIT, FLT3, and RET Receptors Toxicol Pathol, December 1, 2008; 36(7): 905 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E.W. Cohen, L. S. Rosen, E. E. Vokes, M. S. Kies, A. A. Forastiere, F. P. Worden, M. A. Kane, E. Sherman, S. Kim, P. Bycott, et al. Axitinib Is an Active Treatment for All Histologic Subtypes of Advanced Thyroid Cancer: Results From a Phase II Study J. Clin. Oncol., October 10, 2008; 26(29): 4708 - 4713. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Pfister, Y. Feng, F. vom Hagen, S. Hoffmann, G. Molema, J.-L. Hillebrands, M. Shani, U. Deutsch, and H.-P. Hammes Pericyte Migration: A Novel Mechanism of Pericyte Loss in Experimental Diabetic Retinopathy Diabetes, September 1, 2008; 57(9): 2495 - 2502. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Heckman, T. Holopainen, M. Wirzenius, S. Keskitalo, M. Jeltsch, S. Yla-Herttuala, S. R. Wedge, J. M. Jurgensmeier, and K. Alitalo The Tyrosine Kinase Inhibitor Cediranib Blocks Ligand-Induced Vascular Endothelial Growth Factor Receptor-3 Activity and Lymphangiogenesis Cancer Res., June 15, 2008; 68(12): 4754 - 4762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Tatar, E. Yoeruek, P. Szurman, K. U. Bartz-Schmidt, A. Adam, K. Shinoda, C. Eckardt, V. Boeyden, C. Claes, G. Pertile, et al. Effect of Bevacizumab on Inflammation and Proliferation in Human Choroidal Neovascularization Arch Ophthalmol, June 1, 2008; 126(6): 782 - 790. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-J. Mourad, G. des Guetz, H. Debbabi, and B. I. Levy Blood pressure rise following angiogenesis inhibition by bevacizumab. A crucial role for microcirculation Ann. Onc., May 1, 2008; 19(5): 927 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S.R. Maharaj, T. E. Walshe, M. Saint-Geniez, S. Venkatesha, A. E. Maldonado, N. C. Himes, K. S. Matharu, S. A. Karumanchi, and P. A. D'Amore VEGF and TGF-{beta} are required for the maintenance of the choroid plexus and ependyma J. Exp. Med., February 18, 2008; 205(2): 491 - 501. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Grothey Biological Therapy and Other Novel Therapies in Early-Stage Disease: Are They Appropriate? Clin. Cancer Res., November 15, 2007; 13(22): 6909s - 6912s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Affara, B. Dunmore, C. Savoie, S. Imoto, Y. Tamada, H. Araki, D. S. Charnock-Jones, S. Miyano, and C. Print Understanding endothelial cell apoptosis: what can the transcriptome, glycome and proteome reveal? Phil Trans R Soc B, August 29, 2007; 362(1484): 1469 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Sennino, B. L. Falcon, D. McCauley, T. Le, T. McCauley, J. C. Kurz, A. Haskell, D. M. Epstein, and D. M. McDonald Sequential Loss of Tumor Vessel Pericytes and Endothelial Cells after Inhibition of Platelet-Derived Growth Factor B by Selective Aptamer AX102 Cancer Res., August 1, 2007; 67(15): 7358 - 7367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Ward, E. Moore, K. Noon, N. Spassil, E. Keenan, T. L. Ivanco, and J. C. LaManna Cerebral angiogenic factors, angiogenesis, and physiological response to chronic hypoxia differ among four commonly used mouse strains J Appl Physiol, May 1, 2007; 102(5): 1927 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R B Bhisitkul Vascular endothelial growth factor biology: clinical implications for ocular treatments. Br J Ophthalmol, December 1, 2006; 90(12): 1542 - 1547. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Betsholtz and A. Armulik Homeostatic functions of vascular endothelial growth factor in adult microvasculature Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H509 - H511. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
