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Title: VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype

Abstract

Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype.

Authors:
 [1];  [2]
  1. Department of Pathology, Beth Israel Deaconess Medical Center, Research North Building, 99 Brookline Avenue, Boston, MA 02215 (United States). E-mail: jnagy@bidmc.harvard.edu
  2. Department of Pathology, Beth Israel Deaconess Medical Center, Research North Building, 99 Brookline Avenue, Boston, MA 02215 (United States). E-mail: dsenger@bidmc.harvard.edu
Publication Date:
OSTI Identifier:
20775341
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 312; Journal Issue: 5; Other Information: DOI: 10.1016/j.yexcr.2005.10.017; PII: S0014-4827(05)00484-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACTIN; GROWTH FACTORS; INFLAMMATION; MORPHOGENESIS; NEOPLASMS; PHENOTYPE

Citation Formats

Nagy, Janice A., and Senger, Donald R.. VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype. United States: N. p., 2006. Web. doi:10.1016/j.yexcr.2005.10.017.
Nagy, Janice A., & Senger, Donald R.. VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype. United States. doi:10.1016/j.yexcr.2005.10.017.
Nagy, Janice A., and Senger, Donald R.. Fri . "VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype". United States. doi:10.1016/j.yexcr.2005.10.017.
@article{osti_20775341,
title = {VEGF-A, cytoskeletal dynamics, and the pathological vascular phenotype},
author = {Nagy, Janice A. and Senger, Donald R.},
abstractNote = {Normal angiogenesis is a complex process involving the organization of proliferating and migrating endothelial cells (ECs) into a well-ordered and highly functional vascular network. In contrast, pathological angiogenesis, which is a conspicuous feature of tumor growth, ischemic diseases, and chronic inflammation, is characterized by vessels with aberrant angioarchitecture and compromised barrier function. Herein we review the subject of pathological angiogenesis, particularly that driven by vascular endothelial growth factor (VEGF-A), from a new perspective. We propose that the serious structural and functional anomalies associated with VEGF-A-elicited neovessels, reflect, at least in part, imbalances in the internal molecular cues that govern the ordered assembly of ECs into three dimensional vascular networks and preserve vessel barrier function. Adopting such a viewpoint widens the focus from solely on specific pro-angiogenic stimuli such as VEGF-A to include a key set of cytoskeletal regulatory molecules, the Rho GTPases, which are known to direct multiple aspects of vascular morphogenesis including EC motility, alignment, multi-cellular organization, as well as intercellular junction integrity. We offer this perspective to draw attention to the importance of endothelial cytoskeletal dynamics for proper neovascularization and to suggest new therapeutic strategies with the potential to improve the pathological vascular phenotype.},
doi = {10.1016/j.yexcr.2005.10.017},
journal = {Experimental Cell Research},
number = 5,
volume = 312,
place = {United States},
year = {Fri Mar 10 00:00:00 EST 2006},
month = {Fri Mar 10 00:00:00 EST 2006}
}