This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 27/1/99    most recent 01.ATV.0000251504.61247.d5v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Inoue, N. Articles by Murohara, T. Search for Related Content PubMed PubMed Citation Articles by Inoue, N. Articles by Murohara, T. Pubmed/NCBI databases Substance via MeSH Medline Plus Health Information Genes and Gene Therapy

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:99.)
© 2007 American Heart Association, Inc.

Vascular Biology

Therapeutic Angiogenesis Using Novel Vascular Endothelial Growth Factor-E/Human Placental Growth Factor Chimera Genes

Natsuo Inoue; Takahisa Kondo; Koichi Kobayashi; Mika Aoki; Yasushi Numaguchi; Masabumi Shibuya; Toyoaki Murohara

From the Department of Cardiology (N.I., T.K., K.K., M.A., Y.N., T.M.), Nagoya University Graduate School of Medicine, and the Department of Cancer Biology (M.S.), The Institute of Medical Science, The University of Tokyo, Japan.

Correspondence to Takahisa Kondo, MD, PhD, Department of Cardiology, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-8550, Japan. E-mail takahisa{at}med.nagoya-u.ac.jp

Background— Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis but causes adverse side effects such as edema or tissue inflammation. VEGF-E, found in the genome of the Orf virus, specifically binds to VEGF receptor-2 and shows mitotic activity on endothelial cells. Recently, we created two forms of VEGF-E and human placental growth factor (PlGF) chimera genes (VEGF-E chimera #9 and VEGF-E chimera #33), which are humanized genes with VEGF-E function but showing less antigenicity.

Methods and Results— We examined potential proangiogenic activities of these chimera genes. Four types of expression plasmids (pCDNA3.1-LacZ, phVEGF-A, pVEGF-Echimera#9, and pVEGF-Echimera#33) were administered in a rat model of hindlimb ischemia. Either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A significantly increased the ratio of ischemic/normal hindlimb blood-flow compared with the control pCDNA3.1-LacZ treated group (by 1.5-fold, 1.5-fold, and 1.4-fold, respectively, P<0.05). Histochemical staining by alkaline phosphatase also revealed that either pVEGF-Echimera#9, pVEGF-Echimera#33, or phVEGF-A increased the capillary density compared with the pCDNA3.1-LacZ treated group (1.4-fold, 1.5-fold, and 1.5-fold, respectively, P<0.05). Furthermore, immunostaining for anti-ED1 revealed that fewer macrophages had infiltrated in both pVEGF-Echimera#9 and pVEGF-Echimera#33 groups compared with the phVEGF-A group (P<0.05).

Conclusions— Novel VEGF-E/human PlGF chimera genes, pVEGF-Echimera#9, and pVEGF-Echimera#33 significantly stimulated angiogenesis in response to tissue ischemia to an almost identical extent to that induced by phVEGF-A with fewer tissue inflammation responses.

Vascular endothelial growth factor-A (VEGF-A) promotes angiogenesis but causes adverse side effects such as edema or tissue inflammation. VEGF-E, found in the genome of the Orf virus, specifically binds to VEGF receptor-2 and shows mitotic activity on endothelial cells. Recently, we created two forms of VEGF-E and human placental growth factor (PlGF) chimera genes (VEGF-E chimera #9 and VEGF-E chimera #33), which are humanized genes with VEGF-E function but showing less antigenicity

Key Words: angiogenesis • gene therapy

This article has been cited by other articles:

				S. Hazarika, M. Angelo, Y. Li, A. J. Aldrich, S. I. Odronic, Z. Yan, J. S. Stamler, and B. H. Annex Myocyte Specific Overexpression of Myoglobin Impairs Angiogenesis After Hind-Limb Ischemia Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2144 - 2150. [Abstract] [Full Text] [PDF]

				J. Ryu, C.-W. Lee, K.-H. Hong, J.-A. Shin, S.-H. Lim, C.-S. Park, J. Shim, K. B. Nam, K.-J. Choi, Y.-H. Kim, et al. Activation of fractalkine/CX3CR1 by vascular endothelial cells induces angiogenesis through VEGF-A/KDR and reverses hindlimb ischaemia Cardiovasc Res, May 1, 2008; 78(2): 333 - 340. [Abstract] [Full Text] [PDF]