Brain-derived neurotrophic factor (BDNF) has been considered a new angiogenesis mediator. ProBDNF, the precursor of BDNF, plays opposite neuronal functions to BDNF, but the role of proBDNF on angiogenesis remains unknown. We found human umbilical vein endothelial cells (HUVEC) expressing BDNF, proBDNF, p75NTR, Sortilin and TrkB. ProBDNF significantly decreased HUVEC viability in MTT assay, and this inhibition was neutralized by anti-proBDNF. Endothelial cell tube formation assay showed that proBDNF significantly inhibits HUVEC angiogenesis in vitro. Matrigel plug assay disclosed that proBDNF also impeded angiogenesis in vivo, while anti-proBDNF greatly facilitated angiogenesis. Immunostaining of CD31 and α-SMA in Matrigel plugs confirmed the inhibitive effect of proBDNF on angiogenesis. In conclusion, proBDNF can act as an angiogenesis inhibitor. It added more evidence to the “Yin-Yang” theory by showing mBDNF is a mediator of angiogenesis as “Yang” and proBDNF works as an angiogenesis inhibitor as “Yin”.
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