Hepatitis C virus-mediated angiogenesis: Molecular mechanisms and therapeutic strategies

Figure 2 Model for hepatitis C virus-mediated hepatic angiogenesis. During the infection with hepatitis C virus (HCV), normal angiogenesis process can be malignant through the deregulation of genes involved in the angiogenic pathway by viral proteins such as core and non-structural protein NS3. HCV infection can enhance angiogenic process via multiple pathways. One of these pathways is initiated by HCV core or NS3 via NF-κB and, cyclooxygenase (COX-2) leading to the activation of vascular endothelial growth factor (VEGF)/PI3K/AKT/mTOR axis. The other pathway is initiated by core and NS3-induced iNOS/NO axis leading to angiogenesis. Further pathway is initiated by HCV-induced suppression of p53-p21 axis leading to the induction of E2F1 that subsequently mediates the activation of ASK1-JNK/p38 that results in the induction of TGF-β leading to the activation of extracellular regulated kinase (ERK) pathway. ERK pathway together with c-Jun-N-terminal kinase (JNK), p38 will be able to trigger the expression of VEGF and subsequently to the promotion of hepatic angiogenesis.