Role of Angiogenesis in the Pathogenesis of NAFLD.

Lin Lei,Haquima Ei Mourabit,Chantal Housset,Axelle Cadoret,Sara Lemoinne

doi:10.3390/jcm10071338

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the leading cause of chronic liver disease, exposing to the risk of liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Angio-genesis is a complex process leading to the development of new vessels from pre-existing vessels. Angiogenesis is triggered by hypoxia and inflammation and is driven by the action of proangiogenic cytokines, mainly vascular endothelial growth factor (VEGF). In this review, we focus on liver angiogenesis associated with NAFLD and analyze the evidence of liver angiogenesis in animal models of NAFLD and in NAFLD patients. We also report the data explaining the role of angiogenesis in the progression of NAFLD and discuss the potential of targeting angiogenesis, notably VEGF, to treat NAFLD.

Highlights

Non-alcoholic fatty liver disease (NAFLD) includes non-alcoholic fatty liver (NAFL) defined by steatosis and non-alcoholic steatohepatitis (NASH) defined by steatosis associated with inflammation and hepatocyte ballooning
The same result was observed with von Willebrandt factor, another classical marker of endothelial cell, in mice fed with a methionine- and choline-deficient (MCD) diet [12]
Nals come fromVEGFR-2, the adipose tissueendothelial which secretes animal models of NAFLD, Cirrhosis is associated with the risk of developing hepatocellular carcinoma (HCC) in all chronic liver diseases including NAFLD

Summary

Introduction

In the context of chronic liver disease, angiogenesis leads to quantitative changes of liver vessels with the emergence of new vessels and consists in qualitative changes of vessels (both pre-existing and new vessels), resulting in a process known as vascular remodeling. Such qualitative vascular changes include dedifferentiation of liver sinusoidal endothelial cells (LSECs), called capillarization, defined by the loss of their fenestrae and the acquisition of a basement membrane [7]. We discuss the potential of targeting angiogenesis to treat patients with NAFLD

Evidence of Angiogenesis in NAFLD

In Animal Models

In Patients

Role of Angiogenesis in the Progression of NAFLD

Mechanisms promoting in extracellular

Angiogenesis as a Potential Therapeutic Target in NAFLD