Developmental Disorders of the Lymphatics

An information blog for disorders of the lymphatics. For all articles, please click on "Archives" - Due to spammers, I will no longer allow comments, sorry.

Tuesday, February 26, 2008

Overexpression of VEGF-C causes transient lymphatic hyperplasia but not increased lymphangiogenesis in regenerating skin

Overexpression of VEGF-C causes transient lymphatic hyperplasia (lymphedema) but not increased lymphangiogenesis in regenerating skin.

Goldman J, Le TX, Skobe M, Swartz MA. Biomedical Engineering Department, Northwestern University, Evanston, Ill, USA.

Correspondence to Dr Melody A. Swartz, Assistant Professor, Institute for Biological Engineering and Biotechnology, School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland. E-mail

Vascular endothelial growth factor (VEGF)-C is necessary for lymphangiogenesis and holds potential for lymphangiogenic therapy in diseases lacking adequate lymphatic drainage. However, the ability of VEGF-C to enhance sustainable, functional lymphatic growth in adult tissues remains unclear. To address this, we evaluated VEGF-C overexpression in adult lymphangiogenesis in regenerating skin. We used a model of mouse tail skin regeneration incorporating a suspension of either VEGF-C overexpressing tumor cells, which provide a continuous supplement of excess VEGF-C to the natural regenerating environment for more than 25 days, or otherwise identical control- transfected tumor cells. We found that excess VEGF-C did not enhance the rate of lymphatic endothelial cell (LEC) migration, the density of lymphatic vessels, or the rate of functionality -- even though lymphatic hyperplasia was present early on. Furthermore, the hyperplasia disappeared when VEGF-C levels diminished, which occurred after 25 days, rendering the lymphatics indistinguishable from those in control groups. In vitro, we showed that whereas cell-derived VEGF- C could induce chemoattraction of LECs across a membrane (which involves amoeboid-like transmigration), it did not increase LEC chemoinvasion within a 3-dimensional fibrin matrix (which requires proteolytic migration). These results suggest that whereas excess VEGF- C may enhance early LEC proliferation and cause lymphatic vessel hyperplasia, it does not augment the physiological rate of migration or functionality, and by itself cannot sustain any lasting effects on lymphatic size, density, or organization in regenerating adult skin.

AHA Journals

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