Hypoxia, angiogenesis and liver fibrogenesis in the progression of chronic liver diseases.
Angiogenesis is a dynamic, hypoxia-stimulated and growth factor-dependent process, and is currently referred to as the formation of new vessels from pre-existing blood vessels. Experimental and clinical studies have unequivocally reported that hepatic angiogenesis, irrespective of aetiology, occurs in conditions of chronic liver diseases (CLDs) characterized by perpetuation of cell injury and death, inflammatory response and progressive fibrogenesis. Angiogenesis and related changes in liver vascular architecture, that in turn concur to increase vascular resistance and portal hypertension and to decrease parenchymal perfusion, have been proposed to favour fibrogenic progression of the disease towards the end-point of cirrhosis. Moreover, hepatic angiogenesis has also been proposed to modulate the genesis of portal-systemic shunts and increase splanchnic blood flow, thus potentially affecting complications of cirrhosis. Hepatic angiogenesis is also crucial for the growth and progression of hepatocellular carcinoma. Recent literature has identified a number of cellular and molecular mechanisms governing the cross-talk between angiogenesis and fibrogenesis, with a specific emphasis on the crucial role of hypoxic conditions and hepatic stellate cells, particularly when activated to the myofibroblast-like pro-fibrogenic phenotype. Experimental anti-angiogenic therapy has been proven to be effective in limiting the progression of CLDs in animal models. From a clinical point of view, anti-angiogenic therapy is currently emerging as a new pharmacologic intervention in patients with advanced fibrosis and cirrhosis.
Paternostro
Claudia
C
David
Ezio
E
Novo
Erica
E
Parola
Maurizio
M
D000818:Animals; D002908:Chronic Disease; D016207:Cytokines / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000503:physiopathology*; D008107:Liver Diseases / Q000503:physiopathology*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D014655:Vascular Resistance / Q000502:physiology
D016207:Cytokines