Lymphatic hyperplasia, VEGF-C upregulation, MMP-9.

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Lymphatic hyperplasia, VEGF-C upregulation, MMP-9.

Postby patoco » Wed Sep 20, 2006 8:37 pm

Secondary lymphedema in the mouse tail: Lymphatic hyperplasia, VEGF-C upregulation, and the protective role of MMP-9.

July 27, 2006

Rutkowski JM, Moya M, Johannes J, Goldman J, Swartz MA.
Institute of Bioengineering, Ecole Polytechnique Federale de Lausanne
(EPFL), Lausanne, Switzerland.

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.

PMID: 16876204 [PubMed - as supplied by publisher] ... med_docsum


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