Antiangiogenic therapy for portal hypertension in liver cirrhosis: Current progress and perspectives

Table 2 Drugs that can inhibit extrahepatic angiogenesis in portal hypertension

Ref.	Drugs	Experimental models	Effects
Fernandez et al[46]	Rapamycin and glivec	Partial portal vein ligation	Downregulates VEGF, VEGFR2, CD31, PDGF, PDGFR-β, and α-SMA
Mejias et al[19]	Sorafenib	Partial portal vein ligation and CCl4-induced cirrhosis	Blocks 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 analogs	Partial portal vein ligation	Reduces VEGF and CD31 expression, splanchnic neovascularization, and portosystemic collateral circulation by blocking SSTR2
Miternique-Grosse et al[55]	Spironolactone	Biliary cirrhosis	Suppresses the effects of aldosterone and the VEGF signal transduction pathway
Lee et al[58]	N-acetylcysteine	Biliary cirrhosis	Reduces oxidative stress, inflammatory cytokine levels, TNF-α, VEGF, VEGFR2, Ang1, CD31 expression, and suppresses Akt/eNOS/NO pathway
Hsu et al[61]	Bosentan and ambrisentan	Biliary cirrhosis	Block endothelin receptors and suppress iNOS, cyclooxygenase 2, VEGF, VEGFR2, and Akt signaling
Schwabl et al[64]	Pioglitazone	Biliary cirrhosis	Downregulates inflammatory genes and NF-κB expression, suppresses angiogenic and pro-inflammatory cytokines, chemokines, and growth factors (VEGF, PDGF, and PIGF)
Li et al[66]	Thalidomide	Biliary cirrhosis	Hinders TNF-α/interleukin-1β production and blocks the TNFα-VEGF-NOS-NO pathway
Hsu et al[67]	Catechins of Camellia sinensis	Biliary cirrhosis	Reduce HIF-1α expression, Akt signaling, and VEGF synthesis
Hsin et al[68]	2’-hydroxyflavonoid	Thioacetamide-induced liver cirrhosis	Downregulates apoptosis
Hsu et al[69]	Curcumin	Biliary cirrhosis	Suppresses VEGF, cyclooxygenase 2, and eNOS

CCl₄: Carbon tetrachloride; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived growth factor receptor; α-SMA: Alpha smooth muscle actin; SSTR2: Somatostatin receptor type 2; TNF-α: Tumor necrosis factor alpha; Ang1: Angiopoietin 1; eNOS: Endothelial nitric oxide synthase; NO: Nitric oxide; iNOS: Inducible nitric oxide synthase; NF-κB: Factor kappa-light-chain-enhancer of activated B cells; PIGF: Placental growth factor; HIF-1α: Hypoxia-inducible factor-1 alpha.