الفهرس 
Introduction and Aim of the workOnly 14 pages are availabe for public view
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Abstract
-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. -Angiogenesis is a key component in numerous physiologic and pathologic responses and has broad impact in many medical and surgical specialties. - Angiogenesis occurs in several organs during multiple physiological conditions such as wound healing, ovulation, menstruation and Liver regeneration. - Angiogenesis is the result of a complex interplay between growth factors, vascular endothelial cells, extracellular matrix molecules, chemokines and cell signalling molecules. It involves vascular endothelial cell activation, proteolytic endothelial basement membrane degradation, extracellular matrix degradation, endothelial cell migration, vascular proliferation, recruitment of pericytes, and deposition of new basement membrane. -Markers that can separate physiological and pathological angiogenesis are urgently needed in order to selectively deliver anti-angiogenic or vascular disrupting agents to diseased tissues, minimizing the potential for side effects. - The study of angiogenesis has clinical applications in numerous fields including peripheral and coronary vascular disease, oncology, hematology, wound healing, dermatology, ophthalmology, and many others. -These studies reveal striking differences between physiological and pathological angiogenesis at the molecular level, and provide new targets to guide the selective delivery of molecular agents to specific anatomical sites, including cancer. -Experimental evidence demonstrates that the promotion of angiogenic processes can have potential therapeutic benefit in ischemic tissue, while the study of anti-angiogenic therapies have yielded several FDA approved additions to chemotherapeutic regimens in the field of oncology. - Liver regeneration is accompanied by intrahepatic angiogenesis. Antiangiogenic treatment using angiostatin inhibits both phenomena. The authors conclude that liver regeneration is, at least in part, an angiogenesis-dependent phenomenon. -In the last decade experimental and clinical studies have described the occurrence of hepatic angiogenesis in a number of different pathophysiological conditions, including those involving inflammatory, fibrotic and ischemic features. -Although angiogenesis is an integral part of tumor progression, it has also been observed in different inflammatory, fibrotic, and ischemic diseases. Cirrhosis does not represent an exception to this rule. -Cirrhosis is currently ranked as the tenth leading cause of death in the Western world. The evolution of cirrhosis is characterised by intrahepatic vascular remodelling, with capillarisation of sinusoids, fibrogenesis and the development of intrahepatic shunts. The association of fibrogenesis and angiogenesis should be regarded as crucial in the modern evaluation of liver disease progression and in the search for therapeutic targets. -Some cellular and molecular mechanisms have been described which regulate the cross-talk between angiogenesis and fibrogenesis and various hepatic cell populations. Hypoxic hepatocytes, SECs, and activated HSCs play a major role. HSCs are believed to represent a crucial crossroad at the interaction between inflammation, angiogenesis, and fibrogenesis.
SUMMARY
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-The accumulation of inflammatory cells and development of fibrosis may increase the resistance of liver tissue to blood flow and oxygen supply, resulting into hypoxia. Hypoxia promotes angiogenesis and modulates the expression of various genes that promote angiogenesis. - One of the most common complications in patients with cirrhosis is the occurrence of portal hypertension, which results out of an increased resistance to blood flow caused by cirrhosis. Its pathophysiology is linked to an increased hepatic and splanchnic neovascularisation. -The formation of new blood vessels is a key mechanism in the pathogenesis of (CLDs), irrespective of their underlying aetiology. They usually progress from hepatocyte damage to inflammation, fibrosis, cirrhosis and in some cases to hepatocellular carcinoma (HCC). During the pathogenesis of CLDs, neovascularisation and establishment of an abnormal angioarchitecture are related to its pathological progression. -The close relationship between the progression of CLDs and angiogenesis emphasises the need for anti-angiogenic therapy as a tool for blocking or slowing down the disease progression. The fact that angiogenesis plays a pivotal role in CLDs gives rise to new opportunities for treating CLDs and its complications. - Antiangiogenic drugs may be employed as an option to prevent or slow down fibrogenic progression and even the mentioned complications of cirrhosis. It should be used with caution and be carefully balanced in patients due to the fact that angiogenesis is a relevant phenomenon in wound healing and excessive blocking of angiogenesis may not represent the desired therapeutic objective. Moreover, the angiogenic effect might be just one manifestation and consequence of the underlying multiple causes of CLDs.
-Hepatic angiogenesis sets an important point in the control of HCC progression; its inhibition is considered a valuable therapeutic approach for HCC treatment. - Because chronic HCV infection is involved in in several critical molecular signaling pathways in HCC, the attention of clinicians and researchers has focused on the role of HCV infection in the regulation of HCC-associated angiogenesis. -The use of anti-angiogenic drugs and, in particular, of those drugs that have been already approved in the treatment of HCC, may represent an attractive alternative therapeutic tool to prevent or significantly slow down fibrosis progression towards cirrhosis, which also represents the main risk factor