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Angiogenesis in liver regeneration and fibrosis: “a double-edged sword”

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Abstract

Angiogenesis, defined as the formation of new microvasculature from preexisting blood vessels and mature endothelial cells, plays a major role in wound healing and scar formation, and it is associated with inflammatory responses. Angiogenesis can occur in physiological conditions, such as during liver regeneration, and in pathological situations, such as during the progression of fibrosis to cirrhosis and also during tumor angiogenesis. Cellular cross-talk among liver sinusoidal endothelial cells (LSECs), hepatic stellate cells and hepatocytes is believed to play an important role in the angiogenesis process during both liver regeneration and development of cirrhosis. In addition to mature endothelial cells, bone marrow (BM)-derived circulating endothelial progenitor cells (EPCs) have been recently identified for their contribution to post-natal vasculogenesis/angiogenesis. In vivo, EPCs are mobilized into the peripheral blood in response to tissue ischemia or traumatic injury, migrate to the sites of injured endothelium and differentiate into mature endothelial cells. In our recent studies, we have explored the role of EPC-mediated angiogenesis in liver regeneration and/or cirrhosis. Results have demonstrated significantly increased endogenous levels of circulating EPCs in cirrhotic patients in comparison to the controls. Also, EPCs from cirrhotic patients have been observed to stimulate substantial angiogenesis by resident LSECs in vitro via paracrine factors such as vascular endothelial growth factor and platelet-derived growth factor. This review gives an overview of the angiogenesis process in liver regeneration and disease and discusses a new mechanism for intrahepatic angiogenesis mediated by BM-derived EPCs.

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Acknowledgements

The corresponding author is grateful to the Director, Institute of Liver and Biliary Sciences, Delhi, for providing the infrastructure and facilities to perform the study of bone marrow-derived endothelial progenitor cells in liver cirrhosis. The author is also thankful to Dr. Ashok Mukopadhyay, National Institute of Immunology, Delhi, for his valuable contributions to the study.

Compliance with Ethical Requirements and Conflict of interest

This article does not contain any studies with human or animal subjects. Savneet Kaur and K. Anita declare that they have no conflict of interests.

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  1. School of Biotechnology, Gautam Buddha University, Greater Noida, 201312, UP, India

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Kaur, S., Anita, K. Angiogenesis in liver regeneration and fibrosis: “a double-edged sword”. Hepatol Int 7, 959–968 (2013). https://doi.org/10.1007/s12072-013-9483-7

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