P38 THE SKIN MICROVASCULATURE REGRESSES BY APOPTOSIS DURING CATAGEN-DEVELOPMENT IN MURINE SKIN

¹Lars Mecklenburg, ²Desmond J. Tobin, ^1,3Sema Sevinc, ³Süleyman Ergün, ¹Ralf Paus; ¹Dept. of Dermatology, and Dept. of Anatomy, ³University Hospital Eppendorf, University of Hamburg, Hamburg, Germany and ² Department of Biomedical Sciences, University of Bradford, Bradford, UK

Alterations of the cutaneous microvasculature have long been observed in association with hair follicle cycling. Recently, we have demonstrated that anagen is associated with the formation of new capillaries from pre-existing blood vessels (J Invest Dermatol 114:909). We now have investigated whether the cyclic regression of the murine hair follicle (catagen) is accompanied by regression of the skin microvasculature and whether these alterations are possibly regulated by the hair follicle itself. By immunohistochemistry and histomorphometry we demonstrate that in C57BL/6 mice the microvessel density and the number of  endothelial cell nuclei decline during catagen development. This decline is based on endothelial cell apoptosis, as shown by TUNEL-staining and TEM. This was associated with a slight decline of VEGF-immunoreactivity, a potent angiogenic factor that is critical for endothelial cell survival, in epithelial and mesenchymal follicular cells. However, there was widespread VEGF expression elsewhere which did not decline substantially during catagen. One VEGF receptor (Flt-1), which induces endothelial tube formation and vascular maintainance, is constantly expressed on blood vessels of the lower horizontal plexus during the entire anagen to telogen transformation. In contrast, expression of Flt-1 can be detected on many cutaneous blood vessels in anagen VI skin but declines during catagen-development, and is absent in late catagen and telogen skin. We conclude that catagen is associated with substantial microvessel regression by apoptosis. Our data suggest that VEGF is important for the temporary maintainance of newly formed blood vessels of the cutaneous microvasculature and that regression of those vessels is partly regulated by the controlled downregulation of the receptor Flt-1.