Plgf-/-enos-/- Mice Show Defective Angiogenesis Associated with Increased Oxidative Stress in Response to Tissue Ischemia.
From: Institute of Genetics and Biophysics Adriano Buzzati-Traverso, Consiglio Nazionale delle Ricerche, Via P. Castellino, 111, Naples 80131, Italy.
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publish Date: May 2006
- ISSN: 1530-6860
- Volume: 20
- Issue: 7
- Pages: 970-2
- Medium: Internet
- Language: English
- Citation (JAMA): Gigante Bruna, Morlino Giulia, Gentile Maria Teresa, et al. Plgf-/-enos-/- Mice Show Defective Angiogenesis Associated with Increased Oxidative Stress in Response to Tissue Ischemia.. FASEB J. May 2006;20:970-2
Abstract
Neo-angiogenesis is a complex phenomenon modulated by the concerted action of several molecular factors. We have generated a congenic line of knockout mice carrying null mutations of both placental growth factor (PlGF) and endothelial nitric oxide synthase (eNOS), two genes that play a pivotal role in the regulation of pathological angiogenesis. In the present study, we describe the phenotype of this new experimental animal model after surgically induced hind-limb ischemia. Plgf-/-, eNos-/-, Plgf-/- eNos-/-, and wild-type C57BL/6J mice were studied. Plgf-/- eNos-/- mice showed the most severe phenotype: self-amputation, and death occurred in up to 47% of the animals studied; in ischemic legs, capillary density was severely reduced; macrophage infiltration and oxidative stress increased as compared to the other groups of animals. These changes were associated with an up-regulation of both inducible NOS (iNOS) expression and vascular endothelial growth factor (VEGF) protein levels in ischemic limbs, and to an increased extent of protein nitration. Our results demonstrate that the deletion of these two genes, Plgf, which acts in synergism with VEGF, and eNos, a downstream mediator of VEGF, determines a significant change in the vascular response to an ischemic stimulus and that oxidative stress within the ischemic tissue represents a crucial factor to maintain tissue homeostasis.
Mesh Headings (Keywords): Animals, Gene Expression Regulation, Enzymologic, Ischemia, Male, Mice, Mice, Knockout, Muscle, Skeletal, Neovascularization, Physiologic, Nitric Oxide Synthase Type II, Oxidative Stress, Phenotype, Pregnancy Proteins, Reactive Oxygen Species, Time Factors
Check for Full Text / PubMed Unique Identifier (PMID): 16608872
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