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Secondary lymphedema in the mouse tail: Lymphatic hyperplasia, VEGF-C upregulation, and the protective role of MMP-9.
- Source :
-
Microvascular research [Microvasc Res] 2006 Nov; Vol. 72 (3), pp. 161-71. Date of Electronic Publication: 2006 Jul 28. - Publication Year :
- 2006
-
Abstract
- Disturbances in the microcirculation can lead to secondary lymphedema, a common pathological condition that, despite its frequency, still lacks a cure. Lymphedema is clinically well described, but while the genetic underpinnings that cause lymphatic malformations and primary lymphedema are being discovered, the pathophysiology and pathobiology of secondary lymphedema remain poorly understood, partly due to the lack of well-described experimental models. Here, we provide a detailed characterization of secondary lymphedema in the mouse tail and correlate the evolution of tissue swelling to changes in tissue architecture, infiltration of immune cells, deposition of lipids, and proliferation and morphology of the lymphatic vessels. We show that sustained swelling leads to lymphatic hyperplasia and upregulation of vascular endothelial growth factor (VEGF)-C, which may exacerbate the edema because the hyperplastic vessels are poorly functional. The onset of lymphatic hyperplasia occurred prior to the onset of lipid accumulation and peak VEGF-C expression. Langerhans dendritic cells were seen in the dermis migrating from the epidermis to the lymphatic capillaries in edematous tissue. Furthermore, these results were consistent between two different normal mouse strains, but swelling was significantly greater in a matrix metalloproteinase (MMP)-9 null strain. Thus, by characterizing this highly reproducible model of secondary lymphedema, we conclude that VEGF-C upregulation and lymphatic hyperplasia resulting from dermal lymphatic ligation and lymphedema leads to decreased drainage function and that MMP-9 may be important in counteracting tissue swelling.
- Subjects :
- Animals
Cell Movement
Collagen metabolism
Dendritic Cells metabolism
Dendritic Cells pathology
Dermis metabolism
Dermis pathology
Disease Models, Animal
Endothelial Cells metabolism
Endothelial Cells pathology
Female
Hyperplasia
Lipid Metabolism
Lymphatic Vessels metabolism
Lymphatic Vessels surgery
Lymphedema genetics
Lymphedema metabolism
Lymphography
Macrophages metabolism
Macrophages pathology
Mice
Mice, Inbred BALB C
Mice, Inbred Strains
Mice, Knockout
Subcutaneous Tissue metabolism
Subcutaneous Tissue pathology
Tail metabolism
Tail surgery
Time Factors
Lymphatic Vessels pathology
Lymphedema pathology
Matrix Metalloproteinase 9 genetics
Tail pathology
Vascular Endothelial Growth Factor C metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0026-2862
- Volume :
- 72
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Microvascular research
- Publication Type :
- Academic Journal
- Accession number :
- 16876204
- Full Text :
- https://doi.org/10.1016/j.mvr.2006.05.009