Published online before print March 27, 2006, doi: 10.1161/01.HYP.0000215207.54689.31
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Hypertension. 2006;47:887.)
© 2006 American Heart Association, Inc.
Original Articles |
Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload
From the Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Mass.
Correspondence to Kenneth Walsh, Molecular Cardiology/Whitaker Cardiovascular Institute, Boston University School of Medicine, 715 Albany St, W611, Boston, MA 02118. E-mail kxwalsh{at}bu.edu
Cardiac hypertrophy is associated with upregulation of vascular endothelial growth factor (VEGF) in the myocardium. Here, we evaluated the effects of a decoy VEGF receptor on heart morphology and function to a murine model of pressure overload hypertrophy. Mice were administered adenoviral vector encoding a decoy VEGF receptor (Ad-Flk), and their hearts were subjected to pressure overload by transverse aortic constriction (TAC). Treatment with Ad-Flk led to a net reduction in capillary density in hearts subjected to TAC. Ad-Flk also led to a reduction in TAC-induced cardiac hypertrophy and promoted left ventricle dilatation and a loss in contractile function. Treatment with Ad-Flk markedly increased myocardial fibrosis and collagen gene upregulation. In contrast, Ad-Flk had no effect on any of these parameters in sham-treated mice. Administration of a VEGF trap reagent diminished pressure overload cardiac hypertrophy and promoted the progression to heart failure but had no effect on sham-treated animals. These findings suggest that VEGF is required to maintain myocardial capillary density and that reductions in the vascular bed are associated with the transition from compensatory hypertrophy to failure.
Key Words: heart failure • remodeling • endothelial growth factors • hypertrophy
Related Article:
Hypertension 2006 47: 827-829.
This article has been cited by other articles:
 |
|
 |
|
  H. J. Bogaard, R. Natarajan, S. C. Henderson, C. S. Long, D. Kraskauskas, L. Smithson, R. Ockaili, J. M. McCord, and N. F. Voelkel Chronic Pulmonary Artery Pressure Elevation Is Insufficient to Explain Right Heart Failure Circulation, November 17, 2009; 120(20): 1951 - 1960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
Y. Oshima, N. Ouchi, M. Shimano, D. R. Pimentel, K. N. Papanicolaou, K. D. Panse, K. Tsuchida, E. Lara-Pezzi, S.-J. Lee, and K. Walsh Activin A and Follistatin-Like 3 Determine the Susceptibility of Heart to Ischemic Injury Circulation, October 20, 2009; 120(16): 1606 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Madonna and R. De Caterina VEGF receptor switching in heart development and disease Cardiovasc Res, October 1, 2009; 84(1): 4 - 6. [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhou, K. Bourcy, and Y. J. Kang Copper-induced regression of cardiomyocyte hypertrophy is associated with enhanced vascular endothelial growth factor receptor-1 signalling pathway Cardiovasc Res, October 1, 2009; 84(1): 54 - 63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Schmidinger and C. C. Zielinski Reply to A. Bamias et al J. Clin. Oncol., May 20, 2009; 27(15): 2569 - 2570. [Full Text] [PDF]
|
|
|
|
 |
|
 J.-X. Chen and A. Stinnett Ang-1 Gene Therapy Inhibits Hypoxia-Inducible Factor-1{alpha} (HIF-1{alpha})-Prolyl-4-Hydroxylase-2, Stabilizes HIF-1{alpha} Expression, and Normalizes Immature Vasculature in db/db Mice Diabetes, December 1, 2008; 57(12): 3335 - 3343. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ouchi, Y. Oshima, K. Ohashi, A. Higuchi, C. Ikegami, Y. Izumiya, and K. Walsh Follistatin-like 1, a Secreted Muscle Protein, Promotes Endothelial Cell Function and Revascularization in Ischemic Tissue through a Nitric-oxide Synthase-dependent Mechanism J. Biol. Chem., November 21, 2008; 283(47): 32802 - 32811. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Schmidinger, C. C. Zielinski, U. M. Vogl, A. Bojic, M. Bojic, C. Schukro, M. Ruhsam, M. Hejna, and H. Schmidinger Cardiac Toxicity of Sunitinib and Sorafenib in Patients With Metastatic Renal Cell Carcinoma J. Clin. Oncol., November 10, 2008; 26(32): 5204 - 5212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Chen, R. Kerkela, and T. Force Mechanisms of Cardiac Dysfunction Associated With Tyrosine Kinase Inhibitor Cancer Therapeutics Circulation, July 1, 2008; 118(1): 84 - 95. [Full Text] [PDF]
|
|
|
|
|
|
Y. Oshima, N. Ouchi, K. Sato, Y. Izumiya, D. R. Pimentel, and K. Walsh Follistatin-Like 1 Is an Akt-Regulated Cardioprotective Factor That Is Secreted by the Heart Circulation, June 17, 2008; 117(24): 3099 - 3108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. May, D. Gilon, V. Djonov, A. Itin, A. Lazarus, O. Gordon, C. Rosenberger, and E. Keshet Transgenic system for conditional induction and rescue of chronic myocardial hibernation provides insights into genomic programs of hibernation PNAS, January 8, 2008; 105(1): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Klubo-Gwiezdzinska, R. Junik, E. Kopczynska, O. Juraniec, and H. Kardymowicz The comparison of serum vascular endothelial growth factor levels between patients with metastatic and non-metastatic thyroid cancer, and patients with nontoxic multinodular goiter Eur. J. Endocrinol., October 1, 2007; 157(4): 521 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Hannigan, J. G. Coles, and S. Dedhar Integrin-Linked Kinase at the Heart of Cardiac Contractility, Repair, and Disease Circ. Res., May 25, 2007; 100(10): 1408 - 1414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Asaumi, Y. Kagaya, M. Takeda, N. Yamaguchi, H. Tada, K. Ito, J. Ohta, T. Shiroto, K. Shirato, N. Minegishi, et al. Protective Role of Endogenous Erythropoietin System in Nonhematopoietic Cells Against Pressure Overload-Induced Left Ventricular Dysfunction in Mice Circulation, April 17, 2007; 115(15): 2022 - 2032. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jiang, C. Reynolds, C. Xiao, W. Feng, Z. Zhou, W. Rodriguez, S. C. Tyagi, J. W. Eaton, J. T. Saari, and Y. J. Kang Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice J. Exp. Med., March 19, 2007; 204(3): 657 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhou, Y. Jiang, and Y. J. Kang A BRIEF COMMUNICATION: Copper Inhibition of Hydrogen Peroxide-Induced Hypertrophy in Embryonic Rat Cardiac H9c2 Cells Experimental Biology and Medicine, March 1, 2007; 232(3): 385 - 389. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Shiojima and K. Walsh Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway Genes & Dev., December 15, 2006; 20(24): 3347 - 3365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Schiekofer, I. Shiojima, K. Sato, G. Galasso, Y. Oshima, and K. Walsh Microarray analysis of Akt1 activation in transgenic mouse hearts reveals transcript expression profiles associated with compensatory hypertrophy and failure Physiol Genomics, October 11, 2006; 27(2): 156 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. I. Levy Microvascular Plasticity and Experimental Heart Failure Hypertension, May 1, 2006; 47(5): 827 - 829. [Full Text] [PDF]
|
|