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Semin Liver Dis 2019; 39(04): 483-501
DOI: 10.1055/s-0039-1693115
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Vascular Targets for the Treatment of Portal Hypertension

Ksenia Brusilovskaya
1   Vienna Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria
2   Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
,
Philipp Königshofer
1   Vienna Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria
2   Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
,
Philipp Schwabl
1   Vienna Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria
2   Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
,
Thomas Reiberger
1   Vienna Hepatic Hemodynamic Lab (HEPEX), Medical University of Vienna, Vienna, Austria
2   Department of Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria
› Author Affiliations
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Publication History

Publication Date:
17 July 2019 (online)

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Abstract

Portal hypertension is the main driver for severe complications in patients with liver cirrhosis. With improved understanding of molecular pathways that promote hepatic vascular remodeling, vasoconstriction, and sinusoidal capillarization potential vascular targets for the treatment of portal hypertension have been identified. Inhibition of vascular endothelial and platelet-derived growth factors–driven angiogenesis has been shown to reduce portal pressure and decrease hepatic inflammation. Angiopoietin/Tie signaling represents additional promising vascular targets in liver disease. The eNOS-NO-sGC-cGMP pathway modulates sinusoidal vasoconstriction and capillarization. Nuclear farnesoid X receptor (FXR) agonists decrease intrahepatic vascular resistance by inhibition of fibrogenesis and sinusoidal remodeling. Statins ameliorate endothelial dysfunction, decrease portal pressure, and reduce fibrogenesis. Anticoagulation with low-molecular heparin or anti-Xa inhibitors improved portal hypertension by deactivation of hepatic stellate cells and potentially via reduction of sinusoidal microthrombosis. This review summarizes important vascular targets for treatment of portal hypertension that have shown promising results in experimental studies.

Keywords

portal hypertension - fibrosis - angiogenesis - sGC - FXR - anticoagulation - statins