The Multikinase Inhibitor Regorafenib Improves Portal Hypertension in Presence and Absence of Cirrhosis in Rats

Uschner, FrankErhard; Nikolova, Ivelina; Klein, S.; Schierwagen, Robert; Strassburg, CP; Trebicka, Jonel

doi:10.1016/s0168-8278(16)01635-4

Cited by 2 publications

(3 citation statements)

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“…Initially, monoclonal antibodies and specific inhibitors of VEGFr2 were used in PH animals showing improvement in portosystemic collateral vessel formation but showing no effect on PP. 81,82 Subsequent preclinical studies investigated oral tyrosine kinase inhibitors that block VEGFr2, such as sorafenib, 83,84 brivanib 84,85 and regorafenib 86 and showed improved PP and systemic shunting in cirrhotic and noncirrhotic rats with PH. Indeed, tyrosine kinase inhibitors have also been shown to decrease liver fibrosis.…”

Section: Vasoprotective Strategiesmentioning

confidence: 99%

Advances in therapeutic options for portal hypertension

Vilaseca

Guixé‐Muntet

Fernández‐Iglesias

et al. 2018

Therap Adv Gastroenterol

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Portal hypertension represents one of the major clinical consequences of chronic liver disease, having a deep impact on patients’ prognosis and survival. Its pathophysiology defines a pathological increase in the intrahepatic vascular resistance as the primary factor in its development, being subsequently aggravated by a paradoxical increase in portal blood inflow. Although extensive preclinical and clinical research in the field has been developed in recent decades, no effective treatment targeting its primary mechanism has been defined. The present review critically summarizes the current knowledge in portal hypertension therapeutics, focusing on those strategies driven by the disease pathophysiology and underlying cellular mechanisms.

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Section: Vasoprotective Strategiesmentioning

confidence: 99%

Advances in therapeutic options for portal hypertension

Vilaseca

Guixé‐Muntet

Fernández‐Iglesias

et al. 2018

Therap Adv Gastroenterol

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“…PDGF signaling in noncirrhotic portohypertensive rats led to reduction of splanchnic neovascularization and in fall of PP, superior mesenteric artery blood flow and portosystemic collateralization-underlining the importance of VEGF/ PDGF-driven angiogenic signaling in PHT. 41 To decipher the role of multiple pathways of angiogenesis in PHT different tyrosine kinase inhibitors (sorafenib, 36,39,57 sunitinib, 32 brivanib, 58,59 and regorafenib 60 ) have been tested in cirrhotic and noncirrhotic PHT rats. Sunitinib (multitargeted tyrosine kinase inhibitor) significantly decreased collagen expression and viability of human HSCs in line with reduction of inflammatory infiltrate, collagen expression, and decrease of PP in cirrhotic rats.…”

Section: Pdgf-driven Angiogenesis and Combined Inhibition Of Vegf/pdgmentioning

confidence: 99%

“…[187][188][189][190][191] Statins Statins present another therapeutic for liver disease and especially for PHT. Results from preclinical and clinical studies suggest that statins increase hepatic NO bioavailability, improve liver sinusoidal endothelial function, and inhibit HSCs activation 60,[192][193][194][195][196][197][198][199][200][201][202] (►Fig. 4).…”

Section: Preclinical Studies With Fxr Agonists In Phtmentioning

confidence: 99%

Vascular Targets for the Treatment of Portal Hypertension

et al. 2019

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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.

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The Multikinase Inhibitor Regorafenib Improves Portal Hypertension in Presence and Absence of Cirrhosis in Rats

Cited by 2 publications

References 0 publications

Advances in therapeutic options for portal hypertension

Advances in therapeutic options for portal hypertension

Vascular Targets for the Treatment of Portal Hypertension

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