Angiotensin-II and vascular endothelial growth factor interaction plays an important role in rat liver fibrosis development

Both angiotensin-II (AT-II) and vascular endothelial growth factor (VEGF) have been shown to play important roles in the progression of liver fibrosis. However, the interaction of AT-II with VEGF in the liver fibrosis has not been elucidated yet. The aim of the current study was to elucidate a possible association between these molecules, especially in conjunction with the hepatic stellate cells (HSC). The effect of AT-II type 1 receptor blocker (ARB) was assessed on several indices of choline-deficient l-amino acid-defined (CDAA)-induced liver fibrogenesis. This ARB significantly suppressed liver fibrosis development along with suppression of the VEGF expression and neovascularization in the liver. In the cultured activated HSC, AT-II induced VEGF in a dose- and time-dependent manner. ARB and LY333531, a protein kinase C (PKC) inhibitor, attenuated this augmentation. These results indicated that AT-II and VEGF interaction played an important role in liver fibrosis development, and that in the activated HSC, AT-II utilized type 1 receptor and PKC as an intracellular signaling pathway to induce VEGF.