|
|
Blood, 1 March 2008, Vol. 111, No. 5, pp. 2647-2656.
Prepublished online as a Blood First Edition Paper on November 9, 2007; DOI 10.1182/blood-2007-08-109710.
Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice
Magdalena Chrzanowska-Wodnicka1,
Anna E. Kraus2,
Daniel Gale1,
Gilbert C. White, II1, and
Jillian VanSluys1
1 Blood Research Institute, BloodCenter of Wisconsin, Milwaukee; and
2 Department of Medicine and Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill
Angiogenesis is the main mechanism of vascular remodeling during late development and, after birth, in wound healing. Perturbations of angiogenesis occur in cancer, diabetes, ischemia, and inflammation. While much progress has been made in identifying factors that control angiogenesis, the understanding of the precise molecular mechanisms involved is incomplete. Here we identify a small GTPase, Rap1b, as a positive regulator of angiogenesis. Rap1b-deficient mice had a decreased level of Matrigel plug and neonatal retinal neovascularization, and aortas isolated from Rap1b-deficient animals had a reduced microvessel sprouting response to 2 major physiological regulators of angiogenesis: vascular endothelial growth factor (VEGF) and basic fibroblasts growth factor (bFGF), indicating an intrinsic defect in endothelial cells. Proliferation of retinal endothelial cells in situ and in vitro migration of lung endothelial cells isolated from Rap1b-deficient mice were inhibited. At the molecular level, activation of 2 MAP kinases, p38 MAPK and p42/44 ERK, important regulators of endothelial migration and proliferation, was decreased in Rap1b-deficient endothelial cells in response to VEGF stimulation. These studies provide evidence that Rap1b is required for normal angiogenesis and reveal a novel role of Rap1 in regulation of proangiogenic signaling in endothelial cells.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
Related Article in Blood Online:
-
Rap1B speeds up angiogenesis
- Fried J. T. Zwartkruis and Johannes L. Bos
Blood 2008 111: 2500-2501.
[Full Text]
[PDF]
This article has been cited by other articles:

|
 |

|
 |
 
A. C. Roman, J. M. Carvajal-Gonzalez, E. M. Rico-Leo, and P. M. Fernandez-Salguero
Dioxin Receptor Deficiency Impairs Angiogenesis by a Mechanism Involving VEGF-A Depletion in the Endothelium and Transforming Growth Factor-{beta} Overexpression in the Stroma
J. Biol. Chem.,
September 11, 2009;
284(37):
25135 - 25148.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Li, M. Stankovic, B. P.-L. Lee, M. Aurrand-Lions, C. N. Hahn, Y. Lu, B. A. Imhof, M. A. Vadas, and J. R. Gamble
JAM-C Induces Endothelial Cell Permeability Through Its Association and Regulation of {beta}3 Integrins
Arterioscler Thromb Vasc Biol,
August 1, 2009;
29(8):
1200 - 1206.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Bonauer, G. Carmona, M. Iwasaki, M. Mione, M. Koyanagi, A. Fischer, J. Burchfield, H. Fox, C. Doebele, K. Ohtani, et al.
MicroRNA-92a Controls Angiogenesis and Functional Recovery of Ischemic Tissues in Mice
Science,
June 26, 2009;
324(5935):
1710 - 1713.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. L. Bailey, P. Kelly, and P. J. Casey
Activation of Rap1 Promotes Prostate Cancer Metastasis
Cancer Res.,
June 15, 2009;
69(12):
4962 - 4968.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. W. McAlees and V. M. Sanders
Hematopoietic Protein Tyrosine Phosphatase Mediates {beta}2-Adrenergic Receptor-Induced Regulation of p38 Mitogen-Activated Protein Kinase in B Lymphocytes
Mol. Cell. Biol.,
February 1, 2009;
29(3):
675 - 686.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Carmona, S. Gottig, A. Orlandi, J. Scheele, T. Bauerle, M. Jugold, F. Kiessling, R. Henschler, A. M. Zeiher, S. Dimmeler, et al.
Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis
Blood,
January 8, 2009;
113(2):
488 - 497.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Chen, M. Yu, A. Podd, R. Wen, M. Chrzanowska-Wodnicka, G. C. White, and D. Wang
A critical role of Rap1b in B-cell trafficking and marginal zone B-cell development
Blood,
May 1, 2008;
111(9):
4627 - 4636.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
U. Fischer, A. Keller, P. Leidinger, S. Deutscher, S. Heisel, S. Urbschat, H.-P. Lenhof, and E. Meese
A Different View on DNA Amplifications Indicates Frequent, Highly Complex, and Stable Amplicons on 12q13-21 in Glioma
Mol. Cancer Res.,
April 1, 2008;
6(4):
576 - 584.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|