| First Author | Gousopoulos E | Year | 2017 |
| Journal | J Invest Dermatol | Volume | 137 |
| Issue | 9 | Pages | 1995-2004 |
| PubMed ID | 28526302 | Mgi Jnum | J:244040 |
| Mgi Id | MGI:5912819 | Doi | 10.1016/j.jid.2017.04.033 |
| Citation | Gousopoulos E, et al. (2017) An Important Role of VEGF-C in Promoting Lymphedema Development. J Invest Dermatol 137(9):1995-2004 |
| abstractText | Secondary lymphedema is a common complication after cancer treatment, but the pathomechanisms underlying the disease remain unclear. Using a mouse tail lymphedema model, we found an increase in local and systemic levels of the lymphangiogenic factor vascular endothelial growth factor (VEGF)-C and identified CD68+ macrophages as a cellular source. Surprisingly, overexpression of VEGF-C in a transgenic mouse model led to aggravation of lymphedema with increased immune cell infiltration and vascular leakage compared with wild-type littermates. Conversely, blockage of VEGF-C by overexpression of soluble VEGF receptor-3 reduced edema development, diminishing inflammation and blood vascular leakage. Similar findings were obtained in a hind limb lymph node excision lymphedema model. Flow cytometry analyses and immunofluorescence stainings in lymphedematic tissue showed that VEGF receptor-3 expression was restricted to lymphatic endothelial cells. Our data suggest that endogenous VEGF-C causes blood vascular leakage and fluid influx into the tissue, thus actively contributing to edema formation. These data may provide the basis for future clinical therapeutic approaches. |
