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 preexisting 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 specifi c emphasis on the crucial role of hypoxic conditions and hepatic stellate cells,particularly when activated to the myofibroblast-like pro-fibrogenic.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.

Inhibition of Pathological Angiogenesis of Chinese Medicine against Liver Fibrosis

Pathological angiogenesis of liver which includes liver sinusoidal capillarization due to lose of fenestraes of liver sinusoidal endothelial cells（LSECs） and formation of new vascular, is a crucial mechanism responsible for origination and development of liver fibrosis and closely involves in the development of cirrhosis and hepatic cancer. Anti-neovascularization medicine such as sorafenib can decrease portosystemic shunts, improve splanchnic hyperdynamic circulation, lower portal hypertension, while it can not be applied in clinic due to its serious toxic and side reactions. Chinese herbal formula can effectively inhibit pathological angiogenesis of liver, improve microcirculation of liver, and decrease the probability of gastrointestinal hemorrhage in cirrhotic patients. Different Chinese herbal formula are of different characteristics on inhibiting pathological angiogenesis in liver fibrosis, which partly explains synergistic effect of different compatibility of Chinese materia medica and opens up good vista for Chinese medicine against liver fibrosis through inhibiting angiogenesis.

Microcirculation of Liver Cancer,Microenvironment of Liver Regeneration,and the Strategy of Chinese Medicine

Microcirculation of liver cancer is the micro-vascular system which comes from the tissue of liver cancer. It can offer the nutritional requirement for accelerating the cancer cell proliferation and metastasis. The intrinsic mechanism of angiogenesis is the key link in the formation of liver cancer microcirculation system. Liver regeneration microenvironment also plays an important role in the construction of liver cancer microcirculation, through the improvement of liver regeneration microenvironment affecting tumor microcirculation is the new strategy of prevention and treatment of liver cancer. In recent years, it is found that many kinds of Chinese medicine can inhibit angiogenesis, decrease the microvessel density, and delay or prevent the development of liver cancer.