Published online before print December 22, 2005, doi: 10.1161/01.RES.0000200740.57764.52
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on ,
Accepted on December 8, 2005
Impaired Angiogenesis in Glutathione Peroxidase-1-Deficient Mice Is Associated With Endothelial Progenitor Cell Dysfunction
Gennaro Galasso ;
From The Whitaker Cardiovascular Institute, Boston University School of Medicine, Mass.
* To whom correspondence should be addressed. E-mail: kxwalsh{at}bu.edu.
Several vascular disease are characterized by elevated levels of reactive oxygen species (ROS). Vascular endothelium is protected from oxidant stress by expressing enzymes such as glutathione peroxidase type 1 (GPx-1). In this study, we investigated the effect of vascular oxidant stress on ischemia-induced neovascularization in a murine model of homozygous deficiency of GPx-1. GPx-1-deficient mice showed impaired revascularization following hindlimb ischemic surgery based on laser Doppler measurements of blood flow and capillary density in adductor muscle. GPx-1-deficient mice also showed an impaired ability to increase endothelial progenitor cell (EPC) levels in response to ischemic injury or subcutaneous administration of vascular endothelial growth factor protein. EPCs isolated from GPx-1-deficient mice showed a reduced ability to neutralize oxidative stress in vitro, which was associated with impaired migration toward vascular endothelial growth factor and increased sensitivity to ROS-induced apoptosis. EPCs isolated from GPx-1-deficient mice were impaired in their ability to promote angiogenesis in wild-type mice, whereas wild-type EPCs were effective in stimulating angiogenesis in GPx-1-deficient mice. These data suggest that EPC dysfunction is a mechanism by which elevated levels of ROS can contribute to vascular disease.
Key words: glutathione peroxidase-1 • hindlimb ischemia • endothelial progenitor cells • angiogenesis
Related Article:
- Inseparably Tied: Functional and Antioxidative Capacity of Endothelial Progenitor Cells
- Judith Haendeler and Stefanie Dimmeler
Circ. Res. 2006 98: 157-158.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  L. Li, H. Okada, G. Takemura, M. Esaki, H. Kobayashi, H. Kanamori, I. Kawamura, R. Maruyama, T. Fujiwara, H. Fujiwara, et al. Sustained Release of Erythropoietin Using Biodegradable Gelatin Hydrogel Microspheres Persistently Improves Lower Leg Ischemia J. Am. Coll. Cardiol., June 23, 2009; 53(25): 2378 - 2388. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Handy, E. Lubos, Y. Yang, J. D. Galbraith, N. Kelly, Y.-Y. Zhang, J. A. Leopold, and J. Loscalzo Glutathione Peroxidase-1 Regulates Mitochondrial Function to Modulate Redox-dependent Cellular Responses J. Biol. Chem., May 1, 2009; 284(18): 11913 - 11921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sorriento, M. Ciccarelli, G. Santulli, A. Campanile, G. G. Altobelli, V. Cimini, G. Galasso, D. Astone, F. Piscione, L. Pastore, et al. The G-protein-coupled receptor kinase 5 inhibits NF{kappa}B transcriptional activity by inducing nuclear accumulation of I{kappa}B{alpha} PNAS, November 18, 2008; 105(46): 17818 - 17823. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhou, H. G. Bohlen, S. J. Miller, and J. L. Unthank NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo Am J Physiol Heart Circ Physiol, September 1, 2008; 295(3): H1008 - H1016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Urao, H. Inomata, M. Razvi, H. W. Kim, K. Wary, R. McKinney, T. Fukai, and M. Ushio-Fukai Role of Nox2-Based NADPH Oxidase in Bone Marrow and Progenitor Cell Function Involved in Neovascularization Induced by Hindlimb Ischemia Circ. Res., July 18, 2008; 103(2): 212 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Xu, P. Czerwinski, M. Hortmann, H.-Y. Sohn, U. Forstermann, and H. Li Protein kinase C {alpha} promotes angiogenic activity of human endothelial cells via induction of vascular endothelial growth factor Cardiovasc Res, May 1, 2008; 78(2): 349 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Levonen, E. Vahakangas, J. K. Koponen, and S. Yla-Herttuala Antioxidant Gene Therapy for Cardiovascular Disease: Current Status and Future Perspectives Circulation, April 22, 2008; 117(16): 2142 - 2150. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Ceradini, D. Yao, R. H. Grogan, M. J. Callaghan, D. Edelstein, M. Brownlee, and G. C. Gurtner Decreasing Intracellular Superoxide Corrects Defective Ischemia-induced New Vessel Formation in Diabetic Mice J. Biol. Chem., April 18, 2008; 283(16): 10930 - 10938. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. F. Van Craenenbroeck, C. J. Vrints, S. E. Haine, K. Vermeulen, I. Goovaerts, V. F. I. Van Tendeloo, V. Y. Hoymans, and V. M. A. Conraads A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile J Appl Physiol, April 1, 2008; 104(4): 1006 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Dulak, J. Deshane, A. Jozkowicz, and A. Agarwal Heme Oxygenase-1 and Carbon Monoxide in Vascular Pathobiology: Focus on Angiogenesis Circulation, January 15, 2008; 117(2): 231 - 241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Kim, A. Lin, R. E. Guldberg, M. Ushio-Fukai, and T. Fukai Essential Role of Extracellular SOD in Reparative Neovascularization Induced by Hindlimb Ischemia Circ. Res., August 17, 2007; 101(4): 409 - 419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Sorrentino, F. H. Bahlmann, C. Besler, M. Muller, S. Schulz, N. Kirchhoff, C. Doerries, T. Horvath, A. Limbourg, F. Limbourg, et al. Oxidant Stress Impairs In Vivo Reendothelialization Capacity of Endothelial Progenitor Cells From Patients With Type 2 Diabetes Mellitus: Restoration by the Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Rosiglitazone Circulation, July 10, 2007; 116(2): 163 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. L.T. Ballard and J. M. Edelberg Stem Cells and the Regeneration of the Aging Cardiovascular System Circ. Res., April 27, 2007; 100(8): 1116 - 1127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum, D. Fraccarollo, S. Thum, M. Schultheiss, A. Daiber, P. Wenzel, T. Munzel, G. Ertl, and J. Bauersachs Differential Effects of Organic Nitrates on Endothelial Progenitor Cells Are Determined by Oxidative Stress Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 748 - 754. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Thum, D. Fraccarollo, M. Schultheiss, S. Froese, P. Galuppo, J. D. Widder, D. Tsikas, G. Ertl, and J. Bauersachs Endothelial Nitric Oxide Synthase Uncoupling Impairs Endothelial Progenitor Cell Mobilization and Function in Diabetes Diabetes, March 1, 2007; 56(3): 666 - 674. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Marumo, H. Uchimura, M. Hayashi, K. Hishikawa, and T. Fujita Aldosterone Impairs Bone Marrow-Derived Progenitor Cell Formation Hypertension, September 1, 2006; 48(3): 490 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Haendeler and S. Dimmeler Inseparably Tied: Functional and Antioxidative Capacity of Endothelial Progenitor Cells Circ. Res., February 3, 2006; 98(2): 157 - 158. [Full Text] [PDF]
|
|