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.

High cholesterol diet modulates macrophage polarization and liver inflammation during early hepatocellular carcinoma progression in zebrafish

“…A short-term feeding of zebrafish larvae with HCD was enough to induce features of NAFLD/NASH human disease such as liver steatosis associated with hepatocyte ballooning effects, and increased myeloid cell responses characteristic of NASH. Importantly, HCD larvae had increased angiogenesis, consistent with previous reports in other models (31)(32)(33). The diet exacerbated the phenotype associated with larval HCC showing a further increase in liver size and angiogenesis.…”

“…S1A). Liver size, a recognized marker for early liver disease progression (20,29) was increased both with a HCD and in the HCC model ( Fig Increased angiogenesis is an important feature of HCC progression (30), and it has also been associated with NAFLD progression in mouse models after long periods of feeding (31)(32)(33). We therefore characterized the vasculature in the liver using an established transgenic line that labels the vasculature,Tg (flk:mcherry) (Suppl.…”

Tie‐ing Up Angiogenesis to Treat Nonalcoholic Steatohepatitis

“…There is increasing interest in the role of angiogenesis in fibrogenic signaling through generation of proangiogenic mediators that perpetuate injury and promote fibrosis (reviewed in Bocca et al). This is a timely development in understanding the underlying mechanisms and pathways that promote progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) with fibrosis and hepatocellular cancer (HCC), given the global impact of these diseases …”

Single-cell transcriptomics reveals zone-specific alterations of liver sinusoidal endothelial cells in cirrhosis

“…Changes in the cellular location of CD31 may influence its detection by flow cytometry or immunolabeling. It should also be noted that the proportion of vascular ECs increases in liver cirrhosis as angiogenesis increases (43) . This was also confirmed by our scRNA-seq analysis ( Figure 4A).…”