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Molecular and Biological Properties of the Vascular Endothelial Growth Factor Family of Proteins

Department of Cardiovascular Research, Genentech, Inc. South San Francisco, California 94080
Department of Molecular Biology, Genentech, Inc. South San Francisco, California 94080

Correspondence: Address requests for reprints to: Napoleone Ferrara, Department of Cardiovascular Research, Genentech, Inc., 460 Point San Bruno Boulevard, South San Francisco, California 94080.

Abstract

I. Introduction: THE establishment of a vascular supply is a critical requirement for cellular inflow of nutrients, outflow of waste products, and gas exchange in most tissues and organs (1). In endocrine glands, the vascularization not only serves such needs but also provides a pathway for the specific secretory products (2, 3). Furthermore, in the anterior pituitary (4–6) and in the adrenal medulla (7, 8), an unusual angioarchitecture, where a portal capillary plexus delivers venous blood originating from an adjacent gland, is intimately involved in the control of the secretory activity. In the adrenal medulla, this vascular design may even determine the ultimate secretory product (8).

Not surprisingly, the cardiovascular system is the first organ system to develop and reach a functional state in an embryo (9–12). In the human, primitive blood vessels appear as early as day 15, and a circulation with a beating heart is already established by the end of the third week.

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				A. Gurlek, M. R. Pittelkow, and R. Kumar Modulation of Growth Factor/Cytokine Synthesis and Signaling by 1{alpha},25-Dihydroxyvitamin D3: Implications in Cell Growth and Differentiation Endocr. Rev., December 1, 2002; 23(6): 763 - 786. [Abstract] [Full Text] [PDF]

				W D. Strain and N. Chaturvedi Review: The renin-angiotensin-aldosterone system and the eye in diabetes Journal of Renin-Angiotensin-Aldosterone System, December 1, 2002; 3(4): 243 - 246. [Abstract] [PDF]

				E S Bamberger and C W Perrett Angiogenesis in epithelian ovarian cancer Mol. Pathol., December 1, 2002; 55(6): 348 - 359. [Abstract] [Full Text] [PDF]

				L. C. Rockwell, S. Pillai, C. E. Olson, and R. D. Koos Inhibition of Vascular Endothelial Growth Factor/Vascular Permeability Factor Action Blocks Estrogen-Induced Uterine Edema and Implantation in Rodents Biol Reprod, December 1, 2002; 67(6): 1804 - 1810. [Abstract] [Full Text] [PDF]

				M. I. Dorrell, E. Aguilar, and M. Friedlander Retinal Vascular Development Is Mediated by Endothelial Filopodia, a Preexisting Astrocytic Template and Specific R-Cadherin Adhesion Invest. Ophthalmol. Vis. Sci., November 1, 2002; 43(11): 3500 - 3510. [Abstract] [Full Text] [PDF]

				G. P. Bernini, A. Moretti, A. G. Bonadio, M. Menicagli, P. Viacava, A. G. Naccarato, P. Iacconi, P. Miccoli, and A. Salvetti Angiogenesis in Human Normal and Pathologic Adrenal Cortex J. Clin. Endocrinol. Metab., November 1, 2002; 87(11): 4961 - 4965. [Abstract] [Full Text] [PDF]

				N. Inoshima, Y. Nakanishi, T. Minami, M. Izumi, K. Takayama, I. Yoshino, and N. Hara The Influence of Dendritic Cell Infiltration and Vascular Endothelial Growth Factor Expression on the Prognosis of Non-Small Cell Lung Cancer Clin. Cancer Res., November 1, 2002; 8(11): 3480 - 3486. [Abstract] [Full Text] [PDF]

				I. Pham, T. Uchida, C. Planes, L. B. Ware, R. Kaner, M. A. Matthay, and C. Clerici Hypoxia upregulates VEGF expression in alveolar epithelial cells in vitro and in vivo Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1133 - L1142. [Abstract] [Full Text] [PDF]

				H. Matsuno, O. Kozawa, N. Yoshimi, S. Akamatsu, A. Hara, H. Mori, K. Okada, S. Ueshima, O. Matsuo, and T. Uematsu Lack of alpha 2-antiplasmin promotes pulmonary heart failure via overrelease of VEGF after acute myocardial infarction Blood, September 18, 2002; 100(7): 2487 - 2493. [Abstract] [Full Text] [PDF]

				R. Ohashi, A. Shimizu, Y. Masuda, H. Kitamura, M. Ishizaki, Y. Sugisaki, and N. Yamanaka Peritubular Capillary Regression during the Progression of Experimental Obstructive Nephropathy J. Am. Soc. Nephrol., July 1, 2002; 13(7): 1795 - 1805. [Abstract] [Full Text] [PDF]

				J.M. Cotton, A. Mathur, Y. Hong, A.S. Brown, J.F. Martin, and J.D. Erusalimsky Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery Eur. Heart J., June 2, 2002; 23(12): 953 - 959. [Abstract] [Full Text] [PDF]

				A. N. Witmer, J. Dai, H. A. Weich, G. F.J.M. Vrensen, and R. O. Schlingemann Expression of Vascular Endothelial Growth Factor Receptors 1, 2, and 3 in Quiescent Endothelia J. Histochem. Cytochem., June 1, 2002; 50(6): 767 - 778. [Abstract] [Full Text] [PDF]

				D. Wang, R. E. Lehman, D. B. Donner, M. R. Matli, R. S. Warren, and M. L. Welton Expression and endocytosis of VEGF and its receptors in human colonic vascular endothelial cells Am J Physiol Gastrointest Liver Physiol, June 1, 2002; 282(6): G1088 - G1096. [Abstract] [Full Text] [PDF]

				S. Vidal, R. V. Lloyd, L. Moya, B. W. Scheithauer, and K. Kovacs Expression and Distribution of Vascular Endothelial Growth Factor Receptor Flk-1 in the Rat Pituitary J. Histochem. Cytochem., April 1, 2002; 50(4): 533 - 540. [Abstract] [Full Text] [PDF]

				E. J. Duh, H. S. Yang, I. Suzuma, M. Miyagi, E. Youngman, K. Mori, M. Katai, L. Yan, K. Suzuma, K. West, et al. Pigment Epithelium-Derived Factor Suppresses Ischemia-Induced Retinal Neovascularization and VEGF-Induced Migration and Growth Invest. Ophthalmol. Vis. Sci., March 1, 2002; 43(3): 821 - 829. [Abstract] [Full Text] [PDF]

				M. Shimpo, U. Ikeda, Y. Maeda, M. Takahashi, H. Miyashita, H. Mizukami, M. Urabe, A. Kume, T. Takizawa, M. Shibuya, et al. AAV-mediated VEGF gene transfer into skeletal muscle stimulates angiogenesis and improves blood flow in a rat hindlimb ischemia model Cardiovasc Res, March 1, 2002; 53(4): 993 - 1001. [Abstract] [Full Text] [PDF]

				C.-H. Kim, Y.-S. Cho, Y.-S. Chun, J.-W. Park, and M.-S. Kim Early Expression of Myocardial HIF-1{alpha} in Response to Mechanical Stresses: Regulation by Stretch-Activated Channels and the Phosphatidylinositol 3-Kinase Signaling Pathway Circ. Res., February 8, 2002; 90 (2): e25 - e33. [Abstract] [Full Text] [PDF]

				R. K. Rauniyar, K. Suzuma, A. L. King, L. P. Aiello, and G. L. King Differential Effects of Bactericidal/Permeability-Increasing Protein (BPI) Analogues on Retinal Neovascularization and Retinal Pericyte Growth Invest. Ophthalmol. Vis. Sci., February 1, 2002; 43(2): 503 - 509. [Abstract] [Full Text] [PDF]

				D. Dantz, J. Bewersdorf, B. Fruehwald-Schultes, W. Kern, W. Jelkmann, J. Born, H. L. Fehm, and A. Peters Vascular Endothelial Growth Factor: A Novel Endocrine Defensive Response to Hypoglycemia J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 835 - 840. [Abstract] [Full Text] [PDF]

				Y. Wu, S. Yakar, L. Zhao, L. Hennighausen, and D. LeRoith Circulating Insulin-like Growth Factor-I Levels Regulate Colon Cancer Growth and Metastasis Cancer Res., February 1, 2002; 62(4): 1030 - 1035. [Abstract] [Full Text] [PDF]

				M. C. A. Duyndam, M. C. G. W. Hilhorst, H. M. M. Schluper, H. M. W. Verheul, P. J. van Diest, G. Kraal, H. M. Pinedo, and E. Boven Vascular Endothelial Growth Factor-165 Overexpression Stimulates Angiogenesis and Induces Cyst Formation and Macrophage Infiltration in Human Ovarian Cancer Xenografts Am. J. Pathol., February 1, 2002; 160(2): 537 - 548. [Abstract] [Full Text] [PDF]

				M. Sato, T. Tanaka, T. Maeno, Y. Sando, T. Suga, Y. Maeno, H. Sato, R. Nagai, and M. Kurabayashi Inducible Expression of Endothelial PAS Domain Protein-1 by Hypoxia in Human Lung Adenocarcinoma A549 Cells . Role of Src Family Kinases-dependent Pathway Am. J. Respir. Cell Mol. Biol., January 1, 2002; 26(1): 127 - 134. [Abstract] [Full Text] [PDF]

				F. Kuwahara, H. Kai, K. Tokuda, R. Shibata, K. Kusaba, N. Tahara, H. Niiyama, T. Nagata, and T. Imaizumi Hypoxia-Inducible Factor-1{alpha}/Vascular Endothelial Growth Factor Pathway for Adventitial Vasa Vasorum Formation in Hypertensive Rat Aorta Hypertension, January 1, 2002; 39(1): 46 - 50. [Abstract] [Full Text] [PDF]

				Y. Hamma-Kourbali, R. Vassy, A. Starzec, V. Le Meuth-Metzinger, O. Oudar, R. Bagheri-Yarmand, G. Perret, and M. Crepin Vascular Endothelial Growth Factor 165 (VEGF165) Activities Are Inhibited by Carboxymethyl Benzylamide Dextran That Competes for Heparin Binding to VEGF165 and VEGF165{middle dot}KDR Complexes J. Biol. Chem., October 19, 2001; 276(43): 39748 - 39754. [Abstract] [Full Text] [PDF]