Hepatic endothelial dysfunction and abnormal angiogenesis: new targets in the treatment of portal hypertension

J Hepatol. 2010 Sep;53(3):558-67. doi: 10.1016/j.jhep.2010.03.021. Epub 2010 Jun 1.

Abstract

Portal hypertension is the main cause of complications in patients with chronic liver disease. Over the past 25 years, progress in the understanding of the pathophysiology of portal hypertension was followed by the introduction of an effective pharmacological therapy, consisting mainly of treatments aimed at correcting the increased splanchnic blood flow. It is only recently that this paradigm has been changed. Progress in our knowledge of the mechanisms of increased resistance to portal blood flow, of the formation of portal-systemic collaterals, and of mechanisms other than vasodilatation maintaining the increased splanchnic blood flow have opened entirely new perspectives for developing more effective treatment strategies. This is the aim of the current review, which focuses on: (a) the modulation of hepatic vascular resistance by correcting the increased hepatic vascular tone due to hepatic endothelial dysfunction, and (b) correcting the abnormal angiogenesis associated with portal hypertension, which contributes to liver inflammation and fibrogenesis, to the hyperkinetic splanchnic circulation, and to the formation of portal-systemic collaterals and varices.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antioxidants / therapeutic use
  • Biopterin / analogs & derivatives
  • Biopterin / therapeutic use
  • Endothelium, Vascular / physiopathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertension, Portal / pathology
  • Hypertension, Portal / physiopathology
  • Hypertension, Portal / therapy*
  • Liver / blood supply
  • Liver / physiopathology
  • Neovascularization, Pathologic
  • Nitric Oxide / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Prostaglandins / metabolism
  • Signal Transduction
  • Splanchnic Circulation / physiology
  • Vascular Resistance

Substances

  • Antioxidants
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Prostaglandins
  • Biopterin
  • Nitric Oxide
  • Prostaglandin-Endoperoxide Synthases
  • sapropterin