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
