Review
Angiogenesis and Fibrogenesis in Chronic Liver Diseases

https://doi.org/10.1016/j.jcmgh.2015.06.011Get rights and content
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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.

Keywords

Hypoxia
Liver Angiogenesis
Liver Fibrogenesis
Myofibroblasts

Abbreviations used in this paper

Akt
protein kinase B
Ang-1
angiopoietin-1
ANGPTL3
angiopoietin-like-3 peptide
CCL2
chemokine ligand 2
CCR
chemokine receptor
CLD
chronic liver disease
eNOS
endothelial nitric oxide synthase
ET-1
endothelin 1
HCC
hepatocellular carcinoma
Hh
Hedgehog
HIF
hypoxia-inducible factor
HSC
hepatic stellate cell
HSC/MFs
myofibroblast-like cells from activated hepatic stellate cells
LSEC
liver sinusoidal endothelial cell
MF
myofibroblast
MP
microparticle
NAFLD
nonalcoholic fatty liver disease
NASH
nonalcoholic steatohepatitis
NO
nitric oxide
PDGF
platelet-derived growth factor
ROS
reactive oxygen species
α-SMA
α-smooth muscle actin
VEGF
vascular endothelial growth factor
VEGF-R2
vascular endothelial growth factor receptor type 2

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Conflicts of interest The authors disclose no conflicts.