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Plgf-/-eNos-/- mice show defective angiogenesis associated with increased oxidative stress in response to tissue ischemia.
- Source :
-
FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2006 May; Vol. 20 (7), pp. 970-2. Date of Electronic Publication: 2006 Apr 11. - Publication Year :
- 2006
-
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.
- Subjects :
- Animals
Gene Expression Regulation, Enzymologic
Ischemia
Male
Mice
Mice, Knockout
Muscle, Skeletal blood supply
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Nitric Oxide Synthase Type II genetics
Nitric Oxide Synthase Type III
Oxidative Stress
Phenotype
Placenta Growth Factor
Pregnancy Proteins genetics
Reactive Oxygen Species metabolism
Time Factors
Neovascularization, Physiologic physiology
Nitric Oxide Synthase Type II metabolism
Pregnancy Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1530-6860
- Volume :
- 20
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publication Type :
- Academic Journal
- Accession number :
- 16608872
- Full Text :
- https://doi.org/10.1096/fj.05-4481fje