title: Angiogenesis and Fibrogenesis in Chronic Liver Diseases.
abstract: Pathologic angiogenesis appears to be intrinsically associated with the fibrogenic progression of chronic liver diseases, which eventually leads to the development of cirrhosis and related complications, including hepatocellular carcinoma. Several laboratories have suggested that this association is relevant for chronic liver disease progression, with angiogenesis proposed to sustain fibrogenesis. This minireview offers a synthesis of relevant findings and opinions that have emerged in the last few years relating liver angiogenesis to fibrogenesis. We discuss liver angiogenesis in normal and pathophysiologic conditions with a focus on the role of hypoxia and hypoxia-inducible factors and assess the evidence supporting a clear relationship between angiogenesis and fibrogenesis. A section is dedicated to the critical interactions between liver sinusoidal endothelial cells and either quiescent hepatic stellate cells or myofibroblast-like stellate cells. Finally, we introduce the unusual, dual (profibrogenic and proangiogenic) role of hepatic myofibroblasts and emerging evidence supporting a role for specific mediators like vasohibin and microparticles and microvesicles.
authors.affiliation: Unit of Experimental Medicine and Clinical Pathology, Department of Clinical and Biological Sciences, School of Medicine, University of Torino, Torino, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bocca
authors.affiliation: Unit of Experimental Medicine and Clinical Pathology, Department of Clinical and Biological Sciences, School of Medicine, University of Torino, Torino, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Novo
authors.affiliation: Unit of Experimental Medicine and Clinical Pathology, Department of Clinical and Biological Sciences, School of Medicine, University of Torino, Torino, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Miglietta
authors.affiliation: Unit of Experimental Medicine and Clinical Pathology, Department of Clinical and Biological Sciences, School of Medicine, University of Torino, Torino, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Parola
keywords: ANGPTL3, angiopoietin-like-3 peptide; Akt, protein kinase B; Ang-1, angiopoietin-1; CCL2, chemokine ligand 2; CCR, chemokine receptor; CLD, chronic liver disease; ET-1, endothelin 1; HCC, hepatocellular carcinoma; HIF, hypoxia-inducible factor; HSC, hepatic stellate cell; HSC/MFs, myofibroblast-like cells from activated hepatic stellate cells; Hh, Hedgehog; Hypoxia; LSEC, liver sinusoidal endothelial cell; Liver Angiogenesis; Liver Fibrogenesis; MF, myofibroblast; MP, microparticle; Myofibroblasts; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; NO, nitric oxide; PDGF, platelet-derived growth factor; ROS, reactive oxygen species; VEGF, vascular endothelial growth factor; VEGF-R2, vascular endothelial growth factor receptor type 2; eNOS, endothelial nitric oxide synthase; α-SMA, α-smooth muscle actin