Direct Intramuscular Injection of Plasmid DNA Encoding Angiopoietin-1 but not Angiopoietin-2 Augments Revascularization in the Rabbit Ischemic Hindlimb

作者: Kou-Gi Shyu , Orit Manor , Meredith Magner , George D. Yancopoulos , Jeffrey M. Isner

DOI: 10.1161/01.CIR.98.19.2081

关键词: HindlimbPathologyEndocrinologyNeovascularizationGenetic transferMedicineAngiopoietin receptorSalineInternal medicineIschemiaLagomorphaCollateral circulation

摘要: Background—Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have recently been identified as ligands for the endothelial cell–specific Tie2 receptor. Little is known regarding impact of these on postnatal neovascularization. Accordingly, we tested hypothesis that gene transfer plasmid DNA encoding Ang1 Ang2 could modulate collateral vessel development in a rabbit model hindlimb ischemia. Methods Results—pAng1* (n=15), pJFE control (no Ang1* insert) (n=9), pAng2 pcDNA3 (n=10), or saline (n=5) was injected intramuscularly into ischemic hindlimb. Collateral limb perfusion were assessed before 30 days after treatment. Calf blood pressure ratio (ischemic to normal hindlimb) increased versus controls (Ang1*, 0.90±0.02; pJFE, 0.76±0.05; saline, 0.77±0.03; P<0.05). Angiographic score higher (P<0.05) pAng1* group (0.63±0.02) than (0.51±0.03) ...

参考文章(44)
J D Wilson, G P Ferguson, H R Seibel, J L Montour, M M Sholley, Mechanisms of neovascularization. Vascular sprouting can occur without proliferation of endothelial cells. Laboratory Investigation. ,vol. 51, pp. 624- 634 ,(1984)
M. C. Puri, J. Rossant, K. Alitalo, A. Bernstein, J. Partanen, THE RECEPTOR TYROSINE KINASE TIE IS REQUIRED FOR INTEGRITY AND SURVIVAL OF VASCULAR ENDOTHELIAL-CELLS The EMBO Journal. ,vol. 14, pp. 5884- 5891 ,(1995) , 10.1002/J.1460-2075.1995.TB00276.X
T. Couffinhal, M. Silver, L. P. Zheng, M. Kearney, J. M. Isner, B. Witzenbichler, Mouse model of angiogenesis. American Journal of Pathology. ,vol. 152, pp. 1667- 1679 ,(1998)
D W Losordo, S Takeshita, S T Rossow, J M Isner, M Kearney, Time course of recombinant protein secretion after liposome-mediated gene transfer in a rabbit arterial organ culture model. Laboratory Investigation. ,vol. 71, pp. 387- 391 ,(1994)
Douglas Hanahan, Signaling Vascular Morphogenesis and Maintenance Science. ,vol. 277, pp. 48- 50 ,(1997) , 10.1126/SCIENCE.277.5322.48
Werner Risau, Mechanisms of angiogenesis Nature. ,vol. 386, pp. 671- 674 ,(1997) , 10.1038/386671A0
T. N. Sato, Y. Qin, C. A. Kozak, K. L. Audus, Tie-1 and tie-2 define another class of putative receptor tyrosine kinase genes expressed in early embryonic vascular system. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 90, pp. 9355- 9358 ,(1993) , 10.1073/PNAS.90.20.9355
Samuel Davis, Thomas H Aldrich, Pamela F Jones, Ann Acheson, Debra L Compton, Vivek Jain, Terence E Ryan, Joanne Bruno, Czeslaw Radziejewski, Peter C Maisonpierre, George D Yancopoulos, Isolation of Angiopoietin-1, a Ligand for the TIE2 Receptor, by Secretion-Trap Expression Cloning Cell. ,vol. 87, pp. 1161- 1169 ,(1996) , 10.1016/S0092-8674(00)81812-7