Vascular Endothelial Growth Factor-A Mediates Ultraviolet B-Induced Impairment of Lymphatic Vessel Function

Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Wolfgang-Pauli-Str. 10, HCI H303, CH-8093 Zurich, Switzerland.
American Journal Of Pathology (Impact Factor: 4.59). 11/2006; 169(4):1496-503. DOI: 10.2353/ajpath.2006.060197
Source: PubMed


UVB irradiation of the skin induces erythema, epidermal hyperplasia, vascular hyperpermeability, and edema formation. Previous studies have revealed that the cutaneous blood vasculature plays a critical role in the mediation of photodamage. In contrast, the role of lymphatic vessels, which play an essential role in the maintenance of tissue fluid balance, in the response to UVB irradiation has remained unknown. We report here that both acute and chronic UVB irradiation of murine skin results in prominent enlargement of lymphatic vessels. Surprisingly, these enlarged lymphatic vessels were functionally impaired and hyperpermeable, as detected by intravital lymphangiography. The expression levels of vascular endothelial growth factor (VEGF)-A but not of the known lymphangiogenesis factors VEGF-C or VEGF-D, were enhanced in UVB-irradiated epidermis. Targeted overexpression of VEGF-A in the epidermis of transgenic mice led to increased enlargement and leakage of lymphatic vessels after acute UVB irradiation, whereas systemic blockade of VEGF-A signaling largely prevented lymphatic vessel abnormalities and photodamage induced by UVB. Together, these findings identify lymphatic vessels as novel targets for UVB-induced cutaneous photodamage and suggest that VEGF-A mediates impairment of lymphatic vessel function, thereby contributing to the adverse effects of UVB irradiation on the skin.

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    • "Adenoviral mediated delivery of VEGF-A to the ear skin of mice leads to the dramatic enlargement of lymphatic vessels and impairment in lymphatic vessel function [12], [13]. Transgenic overexpression of VEGF-A in the skin of mice also causes lymphatic vessels to preferentially increase in caliber rather than number during settings of inflammation [14], [15]. Conversely, VEGF-A expression in the skin of mice induces sprouting hemangiogenesis resulting in an increase in density of blood vessels [13]. "
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    PLoS ONE 12/2011; 6(12):e28947. DOI:10.1371/journal.pone.0028947 · 3.23 Impact Factor
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    • "Indeed, inhibition of VEGFR-3 signaling has been found to impair the lymphatic vascular network and to promote mucosal edema in a mouse model of chronic airway inflammation (Baluk et al. 2005). Further experimental studies and observations in human inflammatory conditions indicate that impaired lymphatic drainage leads to the exacerbation of disease (Kajiya et al. 2007; Middel et al. 2006; Ryan 1980). VEGF- A and VEGF-C appear to exert opposing effects in chronic inflammation (Halin et al. 2007; Kajiya et al. 2006, 2007). "
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