© 1995 American Heart Association, Inc.
Articles |
Expression of Vascular Endothelial Growth Factor From a Defective Herpes Simplex Virus Type 1 Amplicon Vector Induces Angiogenesis in Mice
From the Department of Medicine (E.A.M., H.J.F., M.B.), Division of Endocrinology, Diabetes Research Center, and the Departments of Neuroscience (H.J.F.), Albert Einstein College of Medicine, Bronx, NY.
Correspondence to Dr Michael Brownlee, Diabetes Research Center, Albert Einstein College of Medicine, Morris Park Ave, F-531, Bronx, NY 10461.
Abstract Vascular endothelial growth factor (VEGF) is a secreted endothelial cell–specific angiogenic growth factor. VEGF gene transfer strategies to stimulate focal angiogenesis could be used to ameliorate myocardial ischemia. To induce angiogenesis in vivo, we have constructed a replication-defective herpes simplex virus type 1 (HSV-1) amplicon vector that places the human VEGF-165 cDNA under the transcriptional control of the HSV immediate-early 4/5 promoter (HSVhvegf). Transduction of NIH 3T3 fibroblasts with HSVhvegf resulted in the secretion of high levels of biologically active VEGF, as assayed by microvascular endothelial mitogenesis. By use of an ex vivo protocol, BLK-CL4 fibroblasts were transduced with HSVhvegf or control HSVlac virus (expressing Escherichia coli ß-galactosidase), resuspended in basement membrane extract (matrigel), and coinjected subcutaneously into syngeneic C57BL/6 mice. One week later, the matrigel plugs with HSVhvegf showed a strong angiogenic response, in contrast to the plugs with HSVlac-transduced fibroblasts. These data indicate that transduction with HSVhvegf virus can induce an angiogenic response in vivo and suggest that this is a viable gene therapy approach for tissue ischemia.
Key Words: lymphokines • DNA virus • gene therapy • endothelium • neovascularization
This article has been cited by other articles:
 |
|
 |
|
  N. Ferrara Vascular Endothelial Growth Factor: Basic Science and Clinical Progress Endocr. Rev., August 1, 2004; 25(4): 581 - 611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Theopold, F. Yao, and E. Eriksson Gene Therapy in the Treatment of Lower Extremity Wounds International Journal of Lower Extremity Wounds, June 1, 2004; 3(2): 69 - 79. [Abstract] [PDF]
|
|
|
|
 |
|
 D. S. Steinbrech, B. J. Mehrara, P. B. Saadeh, J. A. Greenwald, J. A. Spector, G. K. Gittes, and M. T. Longaker VEGF expression in an osteoblast-like cell line is regulated by a hypoxia response mechanism Am J Physiol Cell Physiol, April 1, 2000; 278(4): C853 - C860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Laham, M. Rezaee, M. Post, D. Novicki, F. W. Sellke, J. D. Pearlman, M. Simons, and D. Hung Intrapericardial Delivery of Fibroblast Growth Factor-2 Induces Neovascularization in a Porcine Model of Chronic Myocardial Ischemia J. Pharmacol. Exp. Ther., February 1, 2000; 292(2): 795 - 802. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Kutubuddin, H. J. Federoff, P. M. Challita-Eid, M. Halterman, B. Day, M. Atkinson, V. Planelles, and J. D. Rosenblatt Eradication of Pre-Established Lymphoma Using Herpes Simplex Virus Amplicon Vectors Blood, January 15, 1999; 93(2): 643 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Laham, M. Simons, M. Tofukuji, D. Hung, and F. W. Sellke MODULATION OF MYOCARDIAL PERFUSION AND VASCULAR REACTIVITY BY PERICARDIAL BASIC FIBROBLAST GROWTH FACTOR: INSIGHT INTO ISCHEMIA-INDUCED REDUCTION IN ENDOTHELIUM-DEPENDENT VASODILATATION J. Thorac. Cardiovasc. Surg., December 1, 1998; 116(6): 1022 - 1028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Melillo, M. Scoccianti, I. Kovesdi, J. Safi Jr, T. Riccioni, and M. C Capogrossi Gene therapy for collateral vessel development Cardiovasc Res, September 1, 1997; 35(3): 480 - 489. [Abstract] [Full Text] [PDF]
|
|