on October 11, 2004
Published online before print October 11, 2004, doi: 10.1161/01.CIR.0000145142.85645.EA
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on April 9, 2004
From the Divisions of Cardiovascular Medicine (J.J., J.P.C.) and Hematology (B.Y.Y.T., G.W., J.H., C.J.K.), Stanford University School of Medicine, Stanford, Calif. * To whom correspondence should be addressed. E-mail: cjkuo{at}stanford.edu.
Background--The purpose of the current study was to examine the contribution of endogenous vascular endothelial growth factor (VEGF) to ischemia-induced angiogenesis and perfusion. Methods and Results--C57BL/6J mice (n=28) were subjected to unilateral hindlimb ischemia after intravenous injection of recombinant adenoviruses (109 plaque-forming units) encoding the ligand-binding ectodomain of VEGF receptor 1 (VEGFR1/Ad Flt1), VEGF receptor 2 (VEGFR2/Ad Flk1-Fc), a control murine IgG2 Conclusions--Systemic, soluble receptor-mediated VEGF inhibition indicates an essential role for endogenous VEGF during postischemic angiogenesis and hindlimb perfusion.
Revised on August 9, 2004
Accepted on August 11, 2004
Adenoviral Gene Transfer With Soluble Vascular Endothelial Growth Factor Receptors Impairs Angiogenesis and Perfusion in a Murine Model of Hindlimb Ischemia
Johannes Jacobi MD,
Fc fragment (Ad Fc), or vehicle (phosphate-buffered saline). Hindlimb perfusion was assessed by both laser Doppler and fluorescent microsphere injection 10 days after surgery. The role of endogenous VEGF in ischemia-induced angiogenesis and arteriogenesis was measured by capillary density and microangiography, respectively. Adenoviral gene transfer with soluble VEGFRs significantly attenuated hindlimb perfusion as assessed by laser Doppler and microsphere analysis (P<0.05). Furthermore, soluble VEGFRs significantly reduced ischemia-induced angiogenesis and collateral growth and inhibited histological recovery of muscle tissue. Adverse events consistent with ongoing vascular insufficiency such as limb necrosis or gangrene were observed only in animals expressing soluble VEGFRs and not in control animals.
Key words: collateral circulation • genetics • ischemia • angiogenesis • perfusion
Related Article:
Circulation 2004 110: 2283-2286.
This article has been cited by other articles:
 |
|
 |
|
  Q. Guo, J. J. Carrero, X. Yu, P. Barany, A. R. Qureshi, M. Eriksson, B. Anderstam, M. Chmielewski, O. Heimburger, P. Stenvinkel, et al. Associations of VEGF and its receptors sVEGFR-1 and -2 with cardiovascular disease and survival in prevalent haemodialysis patients Nephrol. Dial. Transplant., November 1, 2009; 24(11): 3468 - 3473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Serrat, D. King, and C. O. Lovejoy Temperature regulates limb length in homeotherms by directly modulating cartilage growth PNAS, December 9, 2008; 105(49): 19348 - 19353. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Clayton, D. Chalothorn, and J. E. Faber Vascular Endothelial Growth Factor-A Specifies Formation of Native Collaterals and Regulates Collateral Growth in Ischemia Circ. Res., October 24, 2008; 103(9): 1027 - 1036. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Oyamada, M. Sone, K. Miyashita, K. Park, D. Taura, M. Inuzuka, T. Sonoyama, H. Tsujimoto, Y. Fukunaga, N. Tamura, et al. The Role of Mineralocorticoid Receptor Expression in Brain Remodeling after Cerebral Ischemia Endocrinology, August 1, 2008; 149(8): 3764 - 3777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hazarika, A. O. Dokun, Y. Li, A. S. Popel, C. D. Kontos, and B. H. Annex Impaired Angiogenesis After Hindlimb Ischemia in Type 2 Diabetes Mellitus: Differential Regulation of Vascular Endothelial Growth Factor Receptor 1 and Soluble Vascular Endothelial Growth Factor Receptor 1 Circ. Res., October 26, 2007; 101(9): 948 - 956. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Limbourg, M. Ploom, D. Elligsen, I. Sorensen, T. Ziegelhoeffer, A. Gossler, H. Drexler, and F. P. Limbourg Notch Ligand Delta-Like 1 Is Essential for Postnatal Arteriogenesis Circ. Res., February 16, 2007; 100(3): 363 - 371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yamaoka-Tojo, T. Tojo, H. W. Kim, L. Hilenski, N. A. Patrushev, L. Zhang, T. Fukai, and M. Ushio-Fukai IQGAP1 Mediates VE-Cadherin-Based Cell-Cell Contacts and VEGF Signaling at Adherence Junctions Linked to Angiogenesis Arterioscler Thromb Vasc Biol, September 1, 2006; 26(9): 1991 - 1997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Izumiya, I. Shiojima, K. Sato, D. B. Sawyer, W. S. Colucci, and K. Walsh Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload Hypertension, May 1, 2006; 47(5): 887 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Toyota, D. C. Warltier, T. Brock, E. Ritman, C. Kolz, P. O'Malley, P. Rocic, M. Focardi, and W. M. Chilian Vascular Endothelial Growth Factor Is Required for Coronary Collateral Growth in the Rat Circulation, October 4, 2005; 112(14): 2108 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yoshida, K. Ohmori, H. Takeuchi, K. Shinomiya, T. Namba, I. Kondo, H. Kiyomoto, and M. Kohno Treatment of Ischemic Limbs Based on Local Recruitment of Vascular Endothelial Growth Factor-Producing Inflammatory Cells With Ultrasonic Microbubble Destruction J. Am. Coll. Cardiol., September 6, 2005; 46(5): 899 - 905. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jacobi, K. Sydow, G. von Degenfeld, Y. Zhang, H. Dayoub, B. Wang, A. J. Patterson, M. Kimoto, H. M. Blau, and J. P. Cooke Overexpression of Dimethylarginine Dimethylaminohydrolase Reduces Tissue Asymmetric Dimethylarginine Levels and Enhances Angiogenesis Circulation, March 22, 2005; 111(11): 1431 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Shiojima and K. Walsh The Role of Vascular Endothelial Growth Factor in Restenosis: The Controversy Continues Circulation, October 19, 2004; 110(16): 2283 - 2286. [Full Text] [PDF]
|
|