Angiogenesis and Fibrosis in Liver Disease

Angiogenesis and fibrosis represent two interlinked processes that underpin the progression of chronic liver disease. Fibrosis arises from sustained hepatocellular injury, triggering activation of hepatic stellate cells and excessive deposition of extracellular matrix components, notably collagen. Concurrently, pathological angiogenesis remodels the sinusoidal vasculature, promoting capillarisation, hypoxia and ongoing inflammation. This vascular remodelling not only sustains fibrogenesis by delivering oxygen and nutrients to activated myofibroblasts, but also facilitates immune cell recruitment and paracrine signalling, thereby reinforcing the cycle of scar formation. Understanding the molecular crosstalk between angiogenic growth factors, hypoxia‐sensing pathways and fibrogenic cell populations is vital for devising therapeutic interventions. By targeting key nodes in these networks, such as tyrosine kinase receptors or oxidative‐stress regulators, it may be possible to halt or even reverse fibrosis and restore hepatic architecture and function.

Research from Nature Portfolio

Studies employing the tyrosine kinase inhibitor Nintedanib have demonstrated significant attenuation of liver fibrosis in preclinical models. In mice subjected to chemical injury, post‐injury administration of this agent reduced collagen accumulation, suppressed activation of hepatic stellate cells and curtailed intrahepatic angiogenesis. Mechanistic investigations revealed that inhibition of fibroblast‐driven paracrine signals diminished macrophage chemotaxis and endothelial tube formation, thereby breaking the feed‐forward loop between inflammation, neovascularisation and scar deposition. These findings establish Nintedanib as a promising candidate for clinical translation in chronic liver disease.

Angiogenesis and Fibrosis in Liver Disease publication trend

The graph below shows the total number of articles in angiogenesis and fibrosis in liver disease across all publications each year (not limited to Nature Index journals).

Technical terms

Angiogenesis: The formation of new blood vessels from existing vasculature, often driven by growth factors in response to hypoxia or injury.

Fibrosis: Excessive accumulation of extracellular matrix proteins, particularly collagen, leading to scar formation and organ dysfunction.

Hepatic stellate cells (HSCs): Liver‐resident pericytes that transdifferentiate into collagen‐secreting myofibroblasts upon activation.

Hypoxia‐inducible factor‐1α (HIF-1α): A transcription factor stabilised under low oxygen tension, regulating genes involved in angiogenesis and metabolism.

Extracellular matrix (ECM): A network of proteins and glycoproteins that provides structural support and biochemical signals to cells within tissues.

References

1. Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis. Journal of Translational Medicine (2024).
2. SH-Alb inhibits phenotype remodeling of pro-fibrotic macrophage to attenuate liver fibrosis through SIRT3-SOD2 axis. Biomedicine & Pharmacotherapy (2024).
3. Tyrosine kinase inhibitor BIBF1120 ameliorates inflammation, angiogenesis and fibrosis in CCl4-induced liver fibrogenesis mouse model. Scientific Reports (2017).