Delphinidin inhibits VEGF induced-mitochondrial biogenesis and Akt activation in endothelial cells

Delphinidin, an anthocyanin present in red wine, has been reported to exert vasculoprotective properties on endothelial cells, including vasorelaxing and anti-apoptotic effects. Moreover, delphinidin treatment in a rat model of post-ischemic neovascularization has been described to exert anti-angiogenic property. Angiogenesis is an energetic process and VEGF-induced angiogenesis is associated with mitochondrial biogenesis. However, whether delphinidin induces changes in mitochondrial biogenesis has never been addressed. Effects of delphinidin were investigated in human endothelial cells at a concentration described to be anti-angiogenic in vitro (10(-2)g/l). mRNA expression of mitochondrial biogenesis factors, mitochondrial respiration, DNA content and enzyme activities were assessed after 48 h of stimulation. Delphinidin increased mRNA expression of several mitochondrial biogenesis factors, including NRF1, ERRα, Tfam, Tfb2m and PolG but did not affect neither mitochondrial respiration, DNA content nor enzyme activities. In presence of delphinidin, VEGF failed to increase mitochondrial respiration, DNA content, complex IV activity and Akt activation in endothelial cells. These results suggest a possible association between inhibition of VEGF-induced mitochondrial biogenesis through Akt pathway by delphinidin and its anti-angiogenic effect, providing a novel mechanism sustaining the beneficial effect of delphinidin against pathologies associated with excessive angiogenesis such as cancers.