Copyright ©The Author(s) 2018.
World J Gastroenterol. Sep 7, 2018; 24(33): 3738-3748
Published online Sep 7, 2018. doi: 10.3748/wjg.v24.i33.3738
Table 1 Drugs that can inhibit intrahepatic angiogenesis in portal hypertension
Ref.DrugsExperimental modelsEffects
Liu et al[15], Qu et al[16], Wang et al[17], Thabut et al[18], Mejias et al[19]SorafenibBiliary cirrhosis, non-alcoholic steatohepatitis, thioacetamide-, diethylnitrosamine-, dimethylnitrosamine-, and CCl4-induced cirrhosisSuppresses the Raf/MEK/ERK signaling pathway and blocks the signaling from the VEGFR, PDGFR, and SCFR; therefore, increases apoptosis and decreases inflammation, fibrogenesis, angiogenesis, and hepatic vascular resistance
Tugues et al[20], Majumder et al[21]SunitinibCCl4-induced cirrhosis and cell cultures (immortalized human activated HSC cell line, human HSC, and isolated primary human liver sinusoidal endothelial cells)Blocks VEGFR1/2/3, PDGFR-α/β, FGFR, and SCFR; reduces HSC collagen synthesis, contractility, cellular migration, and SEC angiogenic capacity
Lin et al[22], Yang et al[23]BrivanibBiliary cirrhosis, non-alcoholic steatohepatitisInhibits VEGFR and FGFR; therefore, suppresses intrahepatic angiogenesis and portal hypertension, improves blood circulation, and hinders ascites formation
Miao et al[31], Marrone et al[32]SimvastatinCCl4-induced cirrhosis and LX-2 cell lineEnhances KLF2, through which deactivates SEC and reduces the severity of fibrosis and associated angiogenesis
Zhu et al[35]RifaximinBiliary cirrhosisDownregulates bacterial lipopolysaccharide binding to TLR4; therefore, reduces the severity of fibrosis and associated angiogenesis
Liu et al[37], Liu et al[38]LargazoleHuman colorectal carcinoma cells (HCT116, HT29, and HCT15), human HSC, and CCl4-induced cirrhosisSuppresses the effects of CD34, VEGF, TGF-β1, and VEGFR2, blocking the main fibrogenic and angiogenic pathways
Michaelis et al[40]RibavirinHuman umbilical vein endothelial cellsHinders angiogenesis by inhibiting inosine-5'-monophosphate dehydrogenase 1, tetrahydrobiopterin, NO, and cGMP
Table 2 Drugs that can inhibit extrahepatic angiogenesis in portal hypertension
Ref.DrugsExperimental modelsEffects
Fernandez et al[46]Rapamycin and glivecPartial portal vein ligationDownregulates VEGF, VEGFR2, CD31, PDGF, PDGFR-β, and α-SMA
Mejias et al[19]SorafenibPartial portal vein ligation and CCl4-induced cirrhosisBlocks VEGF, PDGF, and Raf/MEK/ERK signaling pathway; therefore, reduces intraorgan and systemic blood flow, splanchnic neovascularization, portosystemic shunting, hepatic vascular resistance, and portal pressure
Woltering et al[49], Mejias et al[50]Somatostatin and its synthetic analogsPartial portal vein ligationReduces VEGF and CD31 expression, splanchnic neovascularization, and portosystemic collateral circulation by blocking SSTR2
Miternique-Grosse et al[55]SpironolactoneBiliary cirrhosisSuppresses the effects of aldosterone and the VEGF signal transduction pathway
Lee et al[58]N-acetylcysteineBiliary cirrhosisReduces oxidative stress, inflammatory cytokine levels, TNF-α, VEGF, VEGFR2, Ang1, CD31 expression, and suppresses Akt/eNOS/NO pathway
Hsu et al[61]Bosentan and ambrisentanBiliary cirrhosisBlock endothelin receptors and suppress iNOS, cyclooxygenase 2, VEGF, VEGFR2, and Akt signaling
Schwabl et al[64]PioglitazoneBiliary cirrhosisDownregulates inflammatory genes and NF-κB expression, suppresses angiogenic and pro-inflammatory cytokines, chemokines, and growth factors (VEGF, PDGF, and PIGF)
Li et al[66]ThalidomideBiliary cirrhosisHinders TNF-α/interleukin-1β production and blocks the TNFα-VEGF-NOS-NO pathway
Hsu et al[67]Catechins of Camellia sinensisBiliary cirrhosisReduce HIF-1α expression, Akt signaling, and VEGF synthesis
Hsin et al[68]2’-hydroxyflavonoidThioacetamide-induced liver cirrhosisDownregulates apoptosis
Hsu et al[69]CurcuminBiliary cirrhosisSuppresses VEGF, cyclooxygenase 2, and eNOS