Abstract
Intercellular crosstalk among various liver cells plays an important role in liver
fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Capillarization of liver
sinusoidal endothelial cells (LSECs) precedes fibrosis and accumulating evidence suggests
that the crosstalk between LSECs and other liver cells is critical in the development
and progression of liver fibrosis. LSECs dysfunction, a key event in the progression
from fibrosis to cirrhosis, and subsequently obstruction of hepatic sinuses and increased
intrahepatic vascular resistance (IHVR) contribute to development of portal hypertension
(PHT) and cirrhosis. More importantly, immunosuppressive tumor microenvironment (TME),
which is closely related to the crosstalk between LSECs and immune liver cells like
CD8+ T cells, promotes advances tumorigenesis, especially HCC. However, the connections
within the crosstalk between LSECs and other liver cells during the progression from
liver fibrosis to cirrhosis to HCC have yet to be discussed.
In this review, we first summarize the current knowledge of how different crosstalk
between LSECs and other liver cells, including hepatocytes, hepatic stellate cells
(HSCs), macrophoges, immune cells in liver and extra cellular matrix (ECM) contribute
to the physiological function and the progrssion from liver fibrosis to cirrhosis,
or even to HCC. Then we examine current treatment strategies for LSECs crosstalk in
liver fibrosis, cirrhosis and HCC.
Keywords
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References
- Liver sinusoidal endothelial cells: physiology and role in liver diseases.J Hepatol. 2017; 66: 212-227
- Cooperation of liver cells in health and disease.Adv Anat Embryol Cell Biol. 2001; 161 (III-XIII): 1-151
- Liver sinusoidal endothelial cells-gatekeepers of hepatic immunity.Nat Rev Gastroenterol Hepatol. 2018; 15: 555-567
- Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis.Gastroenterology. 2000; 119: 794-805
- S-adenosyl-L-methionine protects the liver against the cholestatic, cytotoxic, and vasoactive effects of leukotriene D4: a study with isolated and perfused rat liver.Hepatology. 1997; 26: 330-335
- Local control of the immune response in the liver.Immunol Rev. 2000; 174: 21-34
- Regulation of sinusoidal perfusion: in vivo methodology and control by endothelins.Semin Liver Dis. 1999; 19: 383-396
- Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid.J Leukoc Biol. 1998; 63: 534-541
- Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice.Proc Natl Acad Sci U S A. 1999; 96: 7088-7092
- Insulin-like growth factors stimulate expression of hepatocyte growth factor but not transforming growth factor beta1 in cultured hepatic stellate cells.Endocrinology. 1997; 138: 4683-4689
- Characterization of hepatocyte-derived mitogenic activity on hepatic stellate cells.Liver. 2000; 20: 157-164
- Hepatic tissue endothelin-1 levels in chronic liver disease correlate with disease severity and ascites.Am J Gastroenterol. 2000; 95: 199-203
- Cytokines and the liver.J Hepatol. 1997; 27: 1120-1132
- The crosstalk between hepatocytes, hepatic macrophages, and hepatic stellate cells facilitates alcoholic liver disease.Cell Metab. 2019; 30: 850-852
- Crosstalk between liver macrophages and surrounding cells in nonalcoholic steatohepatitis.Front Immunol. 2020; 11: 1169
- Sinusoidal communication in liver fibrosis and regeneration.J Hepatol. 2016; 5: 608-617
- SECs (sinusoidal endothelial cells), liver microenvironment, and fibrosis.Biomed Res Int. 2017; 20174097205
- Intercellular crosstalk of hepatic stellate cells in liver fibrosis: new insights into therapy.Pharmacol Res. 2020; 155104720
- Hepatic stellate cell-macrophage crosstalk in liver fibrosis and carcinogenesis.Semin Liver Dis. 2020; 40: 307-320
- An electron microscopic study of the fenestrated endothelial lining of rat liver sinusoids.J Ultrastruct Res. 1970; 31: 125-150
- The liver sieve: considerations concerning the structure and function of endothelial fenestrae, the sinusoidal wall and the space of Disse.Hepatology. 1985; 5: 683-692
- Structural and functional aspects of liver sinusoidal endothelial cell fenestrae: a review.Comp Hepatol. 2002; 1: 1
- Multimodal superresolution optical microscopy visualizes the close connection between membrane and the cytoskeleton in liver sinusoidal endothelial cell fenestrations.Sci Rep. 2015; 5: 16279
- Increased intrahepatic resistance in severe steatosis: endothelial dysfunction, vasoconstrictor overproduction and altered microvascular architecture.Lab Invest. 2012; 92: 1428-1439
- Actin-spectrin scaffold supports open fenestrae in liver sinusoidal endothelial cells.Traffic. 2019; 20: 932-942
- Hepatic sinusoidal pseudocapillarization with aging in the non-human primate.Exp Gerontol. 2003; 38: 1101-1107
- Age-related pseudocapillarization of the human liver.J Pathol. 2003; 200: 112-117
- The liver sinusoidal endothelial cell: a cell type of controversial and confusing identity.Am J Physiol Gastrointest Liver Physiol. 2008; 294: G391-G400
- Lipoproteins and the liver sieve: the role of the fenestrated sinusoidal endothelium in lipoprotein metabolism, atherosclerosis, and cirrhosis.Hepatology. 1995; 21: 863-874
- LSEC fenestrae are preserved despite pro-inflammatory phenotype of liver sinusoidal endothelial cells in mice on high fat diet.Front Physiol. 2019; 10: 6
- Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance.Aging Cell. 2016; 15: 706-715
- Liver sinusoidal endothelial cells in hepatic fibrosis.Hepatology. 2015; 61: 1740-1746
- Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation.Am J Physiol Gastrointest Liver Physiol. 2004; 287: G757-G763
- A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/Flk-1).Oncogene. 1994; 9: 2683-2690
- Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats.Gastroenterology. 2012; 142 (e6): 918-927
- Liver Sinusoidal Endothelial Cell: An Update.Semin Liver Dis. 2017; 37: 377-387
- Liver sinusoidal endothelial cells.Compr Physiol. 2015; 5: 1751-1774
- Basement membrane type IV collagen and laminin: an overview of their biology and value as fibrosis biomarkers of liver disease.Anat Rec (Hoboken). 2017; 300: 1371-1390
- Bone morphogenetic protein 9 is a paracrine factor controlling liver sinusoidal endothelial cell fenestration and protecting against hepatic fibrosis.Hepatology. 2019; 70: 1392-1408
- Differential consequences of Bmp9 deletion on sinusoidal endothelial cell differentiation and liver fibrosis in 129/Ola and C57BL/6 Mice.Cells. 2019; 8: 1079
- Rat hepatic sinusoidal endothelial cells in monolayer culture. Biochemical and ultrastructural characteristics.J Hepatol. 1988; 6: 23-35
- Biologically active products of stimulated liver macrophages(Kupffer cells).Eur J Biochem. 1990; 192: 245-261
- Identification of prostaglandin F-producing cells in the liver.Histochem Cell Biol. 1999; 112: 451-456
- Prostanoid secretion by rat hepatic sinusoidal endothelial cells and its regulation by exogenous adenosine triphosphate.Hepatology. 1995; 21: 1713-1718
- Potential role for prostaglandin F2 alpha, D2, E2 and thromboxane A2 in mediating the metabolic and hemodynamic actions of sympathetic nerves in perfused rat liver.Eur J Biochem. 1988; 175: 45-50
- Hormonal control of glycogenolysis in parenchymal liver cells by Kupffer and endothelial liver cells.J Biol Chem. 1988; 263: 2699-2703
- Eicosanoid-mediated contractility of hepatic stellate cells.Biochem J. 1992; 285: 367-371
- Leukotriene C4 metabolism during its action on glucose and lactate balance and flow in perfused rat liver.Bioi Chern Hoppe Seyler. 1988; 369: 1131-1136
- S-adenosyl-L-methionine protects the liver against the cholestatic, cytotoxic, and vasoactive effects ofleukotriene D4: a study with isolated and perfused rat liver.Hepatology. 1997; 26: 330-335
- Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis.Gastroenterology. 2000; 119: 794-805
- Rat hepatocytes generate peptide leukotrienes from leukotriene A4.Arch Biochem Biophys. 1993; 305: 378-384
- Stimulation of DNA synthesis and proliferation by prostaglandins in primary cultures of adult rat hepatocytes.Eur J Pharm. 2000; 404: 259-271
- Regulation of the proliferation of primary rat hepatocytes by eicosanoids.J Cell Physiol. 1988; 135: 516-520
- Direct regulation of bile secretion by prostaglandins in perfused rat liver.Hepatology. 1994; 19: 1208-1213
- Nitric oxide in liver injury.Hepatology. 1999; 30: 1-5
- Reduced nitric oxide production by endothelial cells in cirrhotic rat liver: endothelial dysfunction in portal hypertension.Gastroenterology. 1998; 114: 344-351
- Flow-mediated endothelial mechanotransduction.Physiol Rev. 1995; 75: 519-560
- Liver sinusoidal endothelial cells are responsible for nitric oxide modulation of resistance in the hepatic sinusoids.J Clin Invest. 1997; 100: 2923-2930
- Liver sinusoidal endothelial cells and liver regeneration.J Clin Invest. 2013; 123: 1861-1866
- Sinusoidal endothelial cells of the liver: fine structure and function in relation to age.J Electron Microsc Tech. 1990; 14: 218-236
- Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration.Nature. 2010; 468: 310-315
- Substance P promotes liver sinusoidal endothelium-mediated hepatic regeneration by NO/HGF regulation.J Interferon Cytokine Res. 2019; 39: 147-154
- Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence.Hepatology. 2008; 48: 920-930
- Rat liver sinusoidal endothelial cell phenotype is maintained by paracrine and autocrine regulation.Am J Physiol Gastrointest Liver Physiol. 2004; 287: G757-G763
- Expression and role of vascular endothelial growth factor in liver regeneration after partial hepatectomy in rats.J Histochem Cytochem. 2001; 49: 121-130
- Increased expressions of vascular endothelial growth factor and its receptors, flt-1 and KDR/flk-1, in regenerating rat liver.Biochem Biophys Res Commun. 1996; 226: 176-179
- Endothelial cell-derived angiopoietin-2 controls liver regeneration as a spatiotemporal rheostat.Science. 2014; 343: 416-419
- HAb18G/CD147 promotes activation of hepatic stellate cells and is a target for antibody therapy of liver fibrosis.J Hepatol. 2012; 57: 1283-1291
- CD147 promotes liver fibrosis progression via VEGF-A/VEGFR2 signalling-mediated cross-talk between hepatocytes and sinusoidal endothelial cells.Clin Sci (Lond). 2015; 129: 699-710
- Anti-apoptotic therapeutic approaches in liver diseases: do they really make sense?.Apoptosis. 2014; 19: 1243-1253
- LECT2, a ligand for Tie1, plays a crucial role in liver fibrogenesis.Cell. 2019; 178 (e20): 1478-1492
- Endothelial leukocyte cell-derived chemotaxin 2/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 signaling in liver fibrosis.Hepatology. 2020; 72: 347-349
- Angiogenesis in the progression from liver fibrosis to cirrhosis and hepatocelluar carcinoma.Expert Rev Gastroenterol Hepatol. 2020; : 1-17
- Fate tracing reveals hepatic stellate cells as dominant contributors to liver fibrosis independent of its aetiology.Nat Commun. 2013; 4: 2823
- Liver fibrosis: mechanistic concepts and therapeutic perspectives.Cells. 2020; 9: 875
- Epigenetic mechanisms in hepatic stellate cell activation during liver fibrosis and carcinogenesis.Int J Mol Sci. 2019; 20: 2507
- Mechanisms of hepatic stellate cell activation.Nat Rev Gastroenterol Hepatol. 2017; 14: 397-411
- Liver fibrosis: Pathophysiology, pathogenetic targets and clinical issues.Mol Aspects Med. 2019; 65: 37-55
- Studies on capillarization of the hepatic sinusoidsin alcoholic liver disease.Alcohol Alcohol Suppl. 1993; 1B: 77-84
- Sumitran-Holgersson S. Capillarization of hepatic sinusoid by liver endothelial cell-reactive autoantibodies in patients with cirrhosis and chronic hepatitis.Am J Pathol. 2003; 163: 1275-1289
- Immunological functions of liver sinusoidal endothelial cells.Cell Mol Immunol. 2016; 13: 347-353
- The Endothelium as a Driver of Liver Fibrosis and Regeneration.Cells. 2020; 9: 929
- Angiogenesis and Fibrogenesis in Chronic Liver Diseases.Cell Mol Gastroenterol Hepatol. 2015; 1: 477-488
- The transcription factor KLF2 mediates hepatic endothelial protection and paracrine endothelial-stellate cell deactivation induced by statins.J Hepatol. 2013; 58: 98-103
- Expression of variant fibronectins in wound healing: cellular source and biological activity of the EIIIA segment in rat hepatic fibrogenesis.J Cell Biol. 1994; 127: 2037-2048
- Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension.Korean J Intern Med. 2018; 33: 453-461
- Update on new aspects of the renin-angiotensin system in hepatic fibrosis and portal hypertension: implications for novel therapeutic options.J Clin Med. 2021; 10: 702
- Fibronectin extra domain-A promotes hepatic stellate cell motility but not differentiation into myofibroblasts.Gastroenterology. 2012; 142 (e3): 928-937
- Hepatic stem cell niches.J Clin Invest. 2013; 123: 1874-1880
- Pericytes in the Liver.Adv Exp Med Biol. 2019; 1122: 153-167
- The CXCL12 (SDF-1)/CXCR4 chemokine axis: Oncogenic properties, molecular targeting, and synthetic and natural product CXCR4 inhibitors for cancer therapy.Chin J Nat Med. 2018; 16: 801-810
- Stromal cell-derived factor-1 (SDF-1) as a target in liver diseases.Am J Physiol Gastrointest Liver Physiol. 2016; 311: G203-G209
- Divergent angiocrine signals from vascular niche balance liver regeneration and fibrosis.Nature. 2014; 505: 97-102
- Cellular and functional loss of liver endothelial cells correlates with poor hepatocyte regeneration in acute-on-chronic liver failure.Hepatol Int. 2019; 13: 777-787
- Exosome adherence and internalization by hepatic stellate cells triggers sphingosine 1-phosphate-dependent migration.J Biol Chem. 2015; 290: 30684-30696
- Delta-like ligand4/DLL4 regulates the capillarization of liver sinusoidal endothelial cell and liver fibrogenesis.Biochim Biophys Acta Mol Cell Res. 2019; 1866: 1663-1675
- Endothelial Notch activation reshapes the angiocrine of sinusoidal endothelia to aggravate liver fibrosis and blunt regeneration in mice.Hepatology. 2018; 68: 677-690
- Delta-Like Ligand 4 Modulates Liver Damage by Down-Regulating Chemokine Expression.Am J Pathol. 2016; 186: 1874-1889
- The endothelin-1 receptor-mediated pathway is not involved in the endothelin-1-induced defenestration of liver sinusoidal endothelial cells.Liver Int. 2006; 26: 1268-1276
- Caveolin-1 mediates endotoxin inhibition of endothelin-1-induced endothelial nitric oxide synthase activity in liver sinusoidal endothelial cells.Am J Physiol Gastrointest Liver Physiol. 2009; 297: G930-G939
- Hedgehog signalling regulates liver sinusoidal endothelial cell capillarisation.Gut. 2013; 62: 299-309
- Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.Gastroenterology. 2009; 136 (e2): 320-330
- Tetramethylpyrazine attenuates sinusoidal angiogenesis via inhibition of hedgehog signaling in liver fibrosis.IUBMB Life. 2017; 69: 115-127
- The many faces of Hedgehog signalling in the liver: recent progress reveals striking cellular diversity and the importance of microenvironments.J Hepatol. 2014; 61: 1449-1450
- Role of liver sinusoidal endothelial cells in non-alcoholic fatty liver disease.J Hepatol. 2019; 70: 1278-1291
- Induction of cytokine production in naive CD4(+) T cells by antigen-presenting murine liver sinusoidal endothelial cells but failure to induce differentiation toward Th1 cells.Gastroenterology. 1999; 116: 1428-1440
- Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance.Nat Med. 2000; 6: 1348-1354
- Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance.Eur J Immunol. 2005; 35: 2970-2981
- In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity.J Immunol. 2010; 185: 2200-2208
- Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis.J Clin Invest. 2015; 125: 501-520
- Ephrin B2/EphB4 pathway in hepatic stellate cells stimulates Erk-dependent VEGF production and sinusoidal endothelial cell recruitment.Am J Physiol Gastrointest Liver Physiol. 2010; 298: G908-G915
- Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis.Proc Natl Acad Sci U S A. 2012; 109: 9448-9453
- Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies.Cell Mol Immunol. 2016; 13: 316-327
- Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.Biochem Pharmacol. 2013; 86: 836-843
- Key role of liver sinusoidal endothelial cells in liver fibrosis.Biosci Trends. 2017; 11: 163-168
- Physiological role of sinusoidal endothelial cells and Kupffer cells and their implication in the pathogenesis of liver injury.J Hepatobiliary Pancreat Surg. 2000; 7: 40-48
- Kupffer cells potentiate liver sinusoidal endothelial cell injury in sepsis by ligating programmed cell death ligand-1.J Leukoc Biol. 2013; 94: 963-970
- Kupffer cells promote T-cell hepatitis by producing CXCL10 and limiting liver sinusoidal endothelial cell permeability.Theranostics. 2020; 10: 7163-7177
- Kupffer cells protect liver sinusoidal endothelial cells from Fas-dependent apoptosis in sepsis by down-regulating gp130.Am J Pathol. 2013; 182: 742-754
- Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression.Lab Invest. 2015; 95: 1130-1144
- Angiogenesis in chronic liver disease and its complications.Liver Int. 2011; 31: 146-162
- Designing a fibrotic microenvironment to investigate changes in human liver sinusoidal endothelial cell function.Acta Biomater. 2015; 24: 220-227
- Cellular sources of extracellular matrix in hepatic fibrosis.Clin Liver Dis. 2008; 12 (viii): 759-768
- Vascular endothelial cell regulation of extracellular matrix collagen: role of nitric oxide.Arterioscler Thromb Vasc Biol. 1998; 18: 717-722
- Role of extracellular matrix in regulating fenestrations of sinusoidal endothelialcells isolated from normal rat liver.Hepatology. 1992; 15: 989-997
- Microenvironmental regulation of the sinusoidal endothelial cell phenotype in vitro.Hepatology. 2009; 50: 920-928
- Extracellular matrix gene expression increases preferentially in rat lipocytes and sinusoidal endothelial cells during hepatic fibrosis in vivo.J Clin Invest. 1990; 86: 1641-1648
- Transforming growth factor-beta1 stimulates the synthesis of basement membrane proteins laminin, collagen type IV and entactin in rat liver sinusoidal endothelial cells.J Hepatol. 1999; 31: 692-702
- Sinusoidal endothelial cells from guinea pig liver synthesize and secrete cellular fibronectin in vitro.Hepatology. 1987; 7: 856-864
- Effects of extracellular matrices on tube formation of cultured rat hepatic sinusoidal endothelial cells.Hepatology. 1995; 22: 969-973
- Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis.Am J Physiol Gastrointest Liver Physiol. 2007; 293: G1147-G1154
- Hepatic and splenic stiffness augmentation assessed with MR elastography in an in vivo porcine portal hypertension model.J Magn Reson Imaging. 2013; 38: 809-815
- Invasive and non-invasive methods for the assessment of fibrosis and disease progression in chronic liver disease.Best Pract Res Clin Gastroenterol. 2011; 25: 291-303
- Extracellular matrix rigidity controls podosome induction in microvascular endothelial cells.Biol Cell. 2013; 105: 46-57
- Extracellular matrix remodeling in 3D: implications in tissue homeostasis and disease progression.Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2018; 10: e1503
- The role of matrix stiffness in regulating cell behavior.Hepatology. 2008; 47: 1394-1400
- Rat liver endothelial cells isolated by anti-CD31 immunomagnetic separation lack fenestrae and sieve plates.Am J Physiol Gastrointest Liver Physiol. 2006; 291: G1187-G1189
- Expression of cell-cell and cell-matrix adhesion proteins by sinusoidal endothelial cells in the normal and cirrhotic human liver.Am J Pathol. 1993; 143: 738-752
- TypeI, II, III, IV, V., and VI collagens serve as extracellular ligands for the isoforms of platelet-derived growth factor (AA, BB, and AB).J Biol Chem. 1996; 271: 26884-26891
- Evolving concepts of liver fibrogenesis provide new diagnostic and therapeutic options.Comp Hepatol. 2007; 6: 7
- Matrix Mechanics as Regulatory Factors and Therapeutic Targets in Hepatic Fibrosis.Int J Biol Sci. 2019; 15: 2509-2521
- Mechanotransduction-modulated fibrotic microniches reveal the contribution of angiogenesis in liver fibrosis.Nat Mater. 2017; 16: 1252-1261
- Biology of portal hypertension.Hepatol Int. 2018; 12: 11-23
- Pathophysiology of portal hypertension.Clin Liver Dis. 2014; 18: 281-291
- New cellular and molecular targets for the treatment of portal hypertension.Hepatol Int. 2015; 9: 183-191
- Angiocrine signaling in the hepatic sinusoids in health and disease.Am J Physiol Gastrointest Liver Physiol. 2016; 311: G246-G251
- Endothelial p300 promotes portal hypertension and hepatic fibrosis through CCL2-mediated angiocrine signaling.Hepatology. 2020 Nov 7; (Online ahead of print)https://doi.org/10.1002/hep.31617
- Endothelial expression of transcription factor Kruppel-like factor 2 and its vasoprotective target genes in the normal and cirrhotic rat liver.Gut. 2011; 60: 517-524
- Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats.J Hepatol. 2007; 46: 1040-1046
- Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase.Hepatology. 2007; 46: 242-253
- KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins.Gut. 2015; 64: 1434-1443
- Regulation of endothelin-1 synthesis by endothelin-converting enzyme-1 during wound healing.J Biol Chem. 1999; 274: 3228-3234
- Fernández-Iglesias A. Hepatic microcirculation and mechanisms of portal hypertension.Nat Rev Gastroenterol Hepatol. 2019; 16: 221-234
- Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis.Cell Mol Gastroenterol Hepatol. 2020; (S2352-345X(20)30206-X)
- Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers.J Hepatol. 2007; 47: 220-227
- Apoptotic body engulfment by a human stellate cell line is profibrogenic.Lab Invest. 2003; 83: 655-663
- Impaired endothelial nitric oxide synthase activity associated with enhanced caveolin binding in experimental cirrhosis in the rat.Gastroenterology. 1999; 117: 1222-1228
- Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis.Hepatology. 2002; 35: 1010-1021
- Cyclooxygenase-2 and vascular endothelial growth factor in chronic hepatitis, cirrhosis and hepatocellular carcinoma.Clin Mol Hepatol. 2012; 18: 287-294
- A transgenic model for conditional induction and rescue of portal hypertension reveals a role of VEGF-mediated regulation of sinusoidal fenestrations.PLoS One. 2011; 6: e21478
- Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis.Gastroenterology. 2012; 143 (e6): 166-176
- Lipid-induced hepatocyte-derived extracellular vesicles regulate hepatic stellate cell via microRNAs targeting PPAR-gamma.Cell Mol Gastroenterol Hepatol. 2015; 1 (e4): 646-663
- Portal myofibroblasts promote vascular remodeling underlying cirrhosis formation through the release of microparticles.Hepatology. 2015; 61: 1041-1055
- Cirrhotic Endothelial Progenitor Cells Enhance Liver Angiogenesis and Fibrosis and Aggravate Portal Hypertension in Bile Duct-Ligated Cirrhotic Rats.Front Physiol. 2020; 11: 617
- Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension.Gastroenterology. 2019; 157 (e9): 193-209
- LSEC stretch promotes fibrosis during hepatic vascular congestion.Nat Rev Gastroenterol Hepatol. 2019; 16: 262-263
- Epidemiology and surveillance for hepatocellular carcinoma: New trends.J Hepatol. 2020; 72: 250-261
- Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.Int J Cancer. 2019; 144: 1941-1953
- The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver.Front Physiol. 2020; 11: 990
Höchst B., Schildberg F.A., Böttcher J., Metzger C., Huss S., Türler A., Overhaus M., Knoblich A., Schneider B., Pantelis D., Kurts C., Kalff J.C., Knolle P., Diehl L. Liver sinusoidal endothelial cells contribute to CD8 T cell tolerance toward circulating carcinoembryonic antigen in mice Hepatology. 2012; 56(5): 1924-1933.
- Observational Study of PD-L1, TGF-beta, and Immune Cell Infiltrates in Hepatocellular Carcinoma.Front Med (Lausanne). 2019; 6: 15
- TGF-β-dependent induction of CD4⁺CD25⁺Foxp3⁺ Tregs by liver sinusoidal endothelial cells.J Hepatol. 2014; 61: 594-599
- Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.Science. 2018; 360: eaan5931
- Vascular adhesion protein-1 and ICAM-1 support the adhesion of tumor-infiltrating lymphocytes to tumor endothelium in human hepatocellular carcinoma.J Immunol. 1998; 160: 3978-3988
- Expression and function of CXC and CC chemokines in human malignant liver tumors: a role for human monokine induced by gamma-interferon in lymphocyte recruitment to hepatocellular carcinoma.Hepatology. 1999; 30: 100-111
- CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.Am J Physiol Gastrointest Liver Physiol. 2017; 313: G138-G149
- Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis.Cancer Res. 2016; 76: 818-830
- Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids.PLoS Biol. 2005; 3: e113
- Precise delivery of obeticholic acid via nanoapproach for triggering natural killer T cell-mediated liver cancer immunotherapy.Acta Pharm Sin B. 2020; 10: 2171-2182
- Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor.J Leukoc Biol. 2010; 87: 713-725
- Myeloid-Derived Suppressor Cells.Cancer Immunol Res. 2017; 5: 3-8
- A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells.Gastroenterology. 2008; 135: 234-243
- On the origin of myeloid-derived suppressor cells.Oncotarget. 2017; 8: 3649-3665
- Getting to the site of inflammation: the leukocyte adhesion cascade updated.Nat Rev Immunol. 2007; 7: 678-689
- Targeting myeloid-derived suppressor cells in the treatment of hepatocellular carcinoma: current state and future perspectives.J Hepatocell Carcinoma. 2019; 6: 71-84
- Role of the Microenvironment in Liver Metastasis: From Pre- to Prometastatic Niches.Clin Cancer Res. 2016; 22: 5971-5982
- The mobilization, recruitment and contribution of bone marrow-derived endothelial progenitor cells to the tumor neovascularization occur at an early stage and throughout the entire process of hepatocellular carcinoma growth.Oncol Rep. 2012; 28: 1217-1224
- An adiponectin receptor, T-cadherin, was selectively expressed in intratumoral capillary endothelial cells in hepatocellular carcinoma: possible cross talk between T-cadherin and FGF-2 pathways.Virchows Arch. 2006; 448: 311-318
- Expression of T-cadherin in tumor cells influences invasive potential of human hepatocellular carcinoma.FASEB J. 2006; 20: 2291-2301
- Endothelial fatty liver binding protein 4: a new targetable mediator in hepatocellular carcinoma related to metabolic syndrome.Oncogene. 2019; 38: 3033-3046
- Emerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis.Biology (Basel). 2020; 9: 395
- Adipocyte fatty acid binding protein levels relate to inflammation and fibrosis in nonalcoholic fatty liver disease.Hepatology. 2009; 49: 1926-1934
- Leukocyte cell derived chemotaxin-2 (Lect2) as a predictor of survival in adult acute liver failure.Transl Gastroenterol Hepatol. 2019; 4: 17
- Leukocyte cell-derived chemotaxin 2 antagonizes MET receptor activation to suppress hepatocellular carcinoma vascular invasion by protein tyrosine phosphatase 1B recruitment.Hepatology. 2014; 59: 974-985
- YAP Orchestrates Heterotypic Endothelial Cell Communication via HGF/c-MET Signaling in Liver Tumorigenesis.Cancer Res. 2020; 80: 5502-5514
- The Function of the HGF/c-Met Axis in Hepatocellular Carcinoma.Front Cell Dev Biol. 2020; 8: 55
- Activation of the HGF/c-MET axis promotes lenvatinib resistance in hepatocellular carcinoma cells with high c-MET expression.Med Oncol. 2020; 37: 24
- Use of Statins in Patients with Chronic Liver Disease and Cirrhosis: Current Views and Prospects.Curr Gastroenterol Rep. 2017; 19: 43
- Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial.Gastroenterology. 2009; 136: 1651-1658
- How to Face Chronic Liver Disease: The Sinusoidal Perspective.Front Med (Lausanne). 2017; 4: 7
- Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells.J Hepatol. 2010; 53: 702-712
- Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis.Am J Gastroenterol. 2017; 112: 1495-1505
- Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C-Related Compensated Cirrhosis.Gastroenterology. 2016; 150 (e1): 430-440
- Statin use in patients with cirrhosis: a retrospective cohort study.Dig Dis Sci. 2014; 59: 1958-1965
- Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells.Mol Cell Biol. 2002; 22: 8467-8477
- Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase.J Biol Chem. 1998; 273: 24266-24271
- Transduction of the liver with activated Akt normalizes portal pressure in cirrhotic rats.Gastroenterology. 2003; 125: 522-531
- Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells.J Clin Invest. 1998; 101: 2711-2719
- Involvement of Rho GTPases in the transcriptional inhibition of preproendothelin-1 gene expression by simvastatin in vascular endothelial cells.Circ Res. 2000; 87: 616-622
- Simvastatin effects on portal-systemic collaterals of portal hypertensive rats.J Gastroenterol Hepatol. 2010; 25: 1401-1409
- Effects of simvastatin on the portal-systemic collateral vascular response to endothelin-1 and shunting degree in portal hypertensive rats.Scand J Gastroenterol. 2013; 48: 831-838
- Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis.Gastroenterology. 2004; 126: 749-755
- A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats.Sci Rep. 2017; 7: 40461
- Pleiotropic effects of statins in the diseases of the liver.World J Gastroenterol. 2016; 22: 6201-6213
- Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells.BMC Gastroenterol. 2015; 15: 22
- Simvastatin suppresses the proangiogenic microenvironment of human hepatic stellate cells via the Kruppel-like factor 2 pathway.Rev Esp Enferm Dig. 2015; 107: 63-71
- Statins exert endothelial atheroprotective effects via the KLF2 transcription factor.J Biol Chem. 2005; 280: 26714-26719
- Cross-talk between autophagy and KLF2 determines endothelial cell phenotype and microvascular function in acute liver injury.J Hepatol. 2017; 66: 86-94
- Pleiotropic Effects of Statins in the Light of Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.Cureus. 2020; 12: e10446
- Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers.Hepatology. 2012; 55: 921-930
- Atorvastatin and rosuvastatin do not prevent thioacetamide induced liver cirrhosis in rats.World J Gastroenterol. 2013; 19: 241-248
- Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients With Cirrhosis.Gastroenterology. 2016; 150 (e3): 1160-1170
- Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial.Dig Liver Dis. 2015; 47: 957-963
- Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension: a proof-of-concept study.Eur J Gastroenterol Hepatol. 2018; 30: 54-59
- Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES.Hepatology. 2016; 64: 47-57
- Statins Reduce the Risk of Cirrhosis and Its Decompensation in Chronic Hepatitis B Patients: A Nationwide Cohort Study.Am J Gastroenterol. 2016; 111: 976-985
- Statin use and the risk of cirrhosis development in patients with hepatitis C virus infection.J Hepatol. 2015; 63: 1111-1117
- Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study.Hepatology. 2017; 66: 896-907
- Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis. A nationwide case-cohort study.Aliment Pharmacol Ther. 2017; 46: 673-680
- Restoration of liver sinusoidal cell phenotypes by statins improves portal hypertension and histology in rats with.NASH. Sci Rep. 2019; 9: 20183
- Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease.Aging Dis. 2019; 10: 684-698
- Endothelial dysfunction in the regulation of cirrhosis and portal hypertension.Liver Int. 2012; 32: 199-213
- Vascular Targets for the Treatment of Portal Hypertension.Semin Liver Dis. 2019; 39: 483-501
- The eNOS cofactor tetrahydrobiopterin improves endothelial dysfunction in livers of rats with CCl4 cirrhosis.Hepatology. 2006; 44: 44-52
- Three-day tetrahydrobiopterin therapy increases in vivo hepatic NOS activity and reduces portal pressure in CCl4 cirrhotic rats.J Hepatol. 2008; 49: 192-197
- Effects of Sapropterin on Portal and Systemic Hemodynamics in Patients With Cirrhosis and Portal Hypertension: A Bicentric Double-Blind Placebo-Controlled Study.Am J Gastroenterol. 2015; 110: 985-992
- Treatment of bile duct-ligated rats with the nitric oxide synthase transcription enhancer AVE 9488 ameliorates portal hypertension.Liver Int. 2008; 28: 331-338
- Treating portal hypertension in cirrhotic rats with AVE 9488.Liver Int. 2009; 29: 1448
- Defective endothelial nitric oxide synthase signaling is mediated by rho-kinase activation in rats with secondary biliary cirrhosis.Hepatology. 2008; 47: 966-977
- Effects of fasudil on the portal and systemic hemodynamics of patients with cirrhosis.J Gastroenterol Hepatol. 2014; 29: 325-329
- Tempol administration, a superoxide dismutase mimetic, reduces hepatic vascular resistance and portal pressure in cirrhotic rats.J Hepatol. 2011; 54: 660-665
- Recombinant human manganese superoxide dismutase reduces liver fibrosis and portal pressure in CCl4-cirrhotic rats.J Hepatol. 2013; 58: 240-246
- Resveratrol improves intrahepatic endothelial dysfunction and reduces hepatic fibrosis and portal pressure in cirrhotic rats.J Hepatol. 2013; 58: 904-910
- Asymmetric dimethylarginine (ADMA) determines the improvement of hepatic endothelial dysfunction by vitamin E in cirrhotic rats.Liver Int. 2012; 32: 48-57
- Effects of N-acetylcysteine administration in hepatic microcirculation of rats with biliary cirrhosis.J Hepatol. 2008; 49: 25-33
- Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats.Liver Int. 2017; 37: 1002-1012
- Mitochondria-targeted antioxidant mitoquinone attenuates liver inflammation and fibrosis in cirrhotic rats.Am J Physiol Gastrointest Liver Physiol. 2020; 318: G298-G304
- Ascorbic acid improves the intrahepatic endothelial dysfunction of patients with cirrhosis and portal hypertension.Hepatology. 2006; 43: 485-491
- Postprandial effects of dark chocolate on portal hypertension in patients with cirrhosis: results of a phase 2, double-blind, randomized controlled trial.Am J Clin Nutr. 2012; 96: 584-590
- Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability.Hepatology. 2008; 47: 1248-1256
- The Role of Oxidative Stress and Antioxidants in Liver Diseases.Int J Mol Sci. 2015; 16: 26087-26124
- Stimulation of the soluble guanylate cyclase (sGC) inhibits fibrosis by blocking non-canonical TGFbeta signalling.Ann Rheum Dis. 2015; 74: 1408-1416
- Soluble guanylyl cyclase stimulation and phosphodiesterase-5 inhibition improve portal hypertension and reduce liver fibrosis in bile duct-ligated rats.United European Gastroenterol J. 2020; 8: 1174-1185
- The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats.Sci Rep. 2018; 8: 9372
- The soluble guanylate cyclase stimulator IW-1973 prevents inflammation and fibrosis in experimental non-alcoholic steatohepatitis.Br J Pharmacol. 2018; 175: 953-967
- Nitric oxide-independent activation of soluble guanylate cyclase by BAY 60-2770 in experimental liver fibrosis.Arzneimittelforschung. 2008; 58: 71-80
- Immunolocalization of farnesoid X receptor (FXR) in mouse tissues using tissue microarray.Acta Histochem. 2008; 110: 86-93
- Liver capsule: FXR agonists against liver disease.Hepatology. 2016; 64: 1773
- Farnesoid X Receptor Agonists and Other Bile Acid Signaling Strategies for Treatment of Liver Disease.Dig Dis. 2016; 34: 580-588
- Hepatic dimethylarginine-dimethylaminohydrolase1 is reduced in cirrhosis and is a target for therapy in portal hypertension.J Hepatol. 2015; 62: 325-331
- Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats.Hepatology. 2014; 59: 2286-2298
- Coordinated regulation of dimethylarginine dimethylaminohydrolase-1 and cationic amino acid transporter-1 by farnesoid X receptor in mouse liver and kidney and its implication in the control of blood levels of asymmetric dimethylarginine.J Pharmacol Exp Ther. 2009; 331: 234-243
- The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction.J Hepatol. 2017; 66: 724-733
- The Non-Steroidal FXR Agonist Cilofexor Improves Portal Hypertension and Reduces Hepatic Fibrosis in a.Rat NASH Model. Biomedicines. 2021; 9: 60
- The Nonsteroidal Farnesoid X Receptor Agonist Cilofexor (GS-9674) Improves Markers of Cholestasis and Liver Injury in Patients With Primary Sclerosing Cholangitis.Hepatology. 2019; 70: 788-801
- A novel non-bile acid FXR agonist EDP-305 potently suppresses liver injury and fibrosis without worsening of ductular reaction.Liver Int. 2020; 40: 1655-1669
- Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis.J Hepatol. 2009; 51: 380-388
- Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mouse cholangiopathy model by promoting biliary HCO⁻₃ output.Hepatology. 2011; 54: 1303-1312
- FXR and TGR5 Agonists Ameliorate Liver Injury, Steatosis, and Inflammation After Binge or Prolonged Alcohol Feeding in Mice.Hepatol Commun. 2018; 2: 1379-1391
- Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodeoxycholic acid.Gastroenterology. 2015; 148 (e8): 751-761
- Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis.Clin Gastroenterol Hepatol. 2020; 18 (e6): 1170-1178
- Long-term efficacy and safety of obeticholic acid for patients with primary biliary cholangitis: 3-year results of an international open-label extension study.Lancet Gastroenterol Hepatol. 2019; 4: 445-453
- Obeticholic acid is associated with improvements in AST-to-platelet ratio index and GLOBE score in patients with primary biliary cholangitis.JHEP Rep. 2020; 3100191
- A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis.N Engl J Med. 2016; 375: 631-643
- Obeticholic Acid PBC Monotherapy Study Group. A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis.Hepatology. 2018; 67: 1890-1902
- Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis.Sci Rep. 2018; 8: 8157
- Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial. NASH Clinical Research Network.Lancet. 2015; 385: 956-965
- Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial.Lancet. 2019; 394: 2184-2196
- REGENERATE: Design of a pivotal, randomised, phase 3 study evaluating the safety and efficacy of obeticholic acid in patients with fibrosis due to nonalcoholic steatohepatitis.Contemp Clin Trials. 2019; 84105803
- Tissue expression, distribution, and regulation of PDE5.Int J Impot Res. 2004; : S8-S10
- Cyclic nucleotide phosphodiesterase (PDE) isozymes as targets of the intracellular signalling network: benefits of PDE inhibitors in various diseases and perspectives for future therapeutic developments.Br J Pharmacol. 2012; 165: 1288-1305
- Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver.BMC Gastroenterol. 2009; 9: 69
- Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients.Liver Int. 2004; 24: 63-68
- Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension.World J Gastroenterol. 2018; 24: 4356-4368
- Acute administration of sildenafil enhances hepatic cyclic guanosine monophosphate production and reduces hepatic sinusoid resistance in cirrhotic patients.Hepatol Res. 2008; 38: 1186-1193
- Sildenafil does not influence hepatic venous pressure gradient in patients with cirrhosis.World J Gastroenterol. 2008; 14: 6208-6212
- Sildenafil has no effect on portal pressure but lowers arterial pressure in patients with compensated cirrhosis.Clin Gastroenterol Hepatol. 2010; 8: 546-549
- Effect of udenafil on portal venous pressure and hepatic fibrosis in rats. A novel therapeutic option for portal hypertension.Arzneimittelforschung. 2009; 59: 641-646
- The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study.Dig Liver Dis. 2015; 47: 144-150
- Effect of vardenafil, an inhibitor of phosphodiesterase-5, on portal haemodynamics in normal and cirrhotic liver – results of a pilot study.Aliment Pharmacol Ther. 2006; 23: 121-128
- Phosphodiesterase 5 inhibitors lower both portal and pulmonary pressure in portopulmonary hypertension: a case report.J Med Case Rep. 2007; 1: 46
- Beneficial long term effect of a phosphodiesterase-5-inhibitor in cirrhotic portal hypertension: A case report with 8 years follow-up.World J Gastroenterol. 2018; 24: 438-444
- Sac-1004, a novel vascular leakage blocker, enhances endothelial barrier through the cAMP/Rac/cortactin pathway.Biochem Biophys Res Commun. 2013; 435: 420-427
- The endothelial dysfunction blocker CU06-1004 ameliorates choline-deficient L-amino acid diet-induced non-alcoholic steatohepatitis in mice.PLoS One. 2020; 15e0243497
- Nitroflurbiprofen, a nitric oxide-releasing cyclooxygenase inhibitor, improves cirrhotic portal hypertension in rats.Gastroenterology. 2007; 132: 709-719
- Cyclooxygenase-1 inhibition corrects endothelial dysfunction in cirrhotic rat livers.J Hepatol. 2003; 39: 515-521
- Arachidonic acid metabolites and endothelial dysfunction of portal hypertension.Prostaglandins Other Lipid Mediat. 2015; 120: 80-90
- Terutroban, a TP-receptor antagonist, reduces portal pressure in cirrhotic rats.Hepatology. 2013; 58: 1424-1435
- Treatment with the leukotriene inhibitor montelukast for 10 days attenuates portal hypertension in rat liver cirrhosis.Hepatology. 2010; 51: 2086-2096
- Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial.Lancet. 2017; 389: 2492-2502
- Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib: The CheckMate 040 Randomized Clinical Trial.JAMA Oncol. 2020; 6e204564
- Nivolumab for the treatment of hepatocellular carcinoma.Expert Opin Biol Ther. 2020; 20: 687-693
- CXCL12 (SDF1alpha)-CXCR4/CXCR7 pathway inhibition: an emerging sensitizer for anticancer therapies?.Clin Cancer Res. 2011; 17: 2074-2080
- CXCR4 inhibition in tumor microenvironment facilitates anti-programmed death receptor-1 immunotherapy in sorafenib-treated hepatocellular carcinoma in mice.Hepatology. 2015; 61: 1591-1602
- Increasing Tumor-Infiltrating T Cells through Inhibition of CXCL12 with NOX-A12 Synergizes with PD-1 Blockade.Cancer Immunol Res. 2017; 5: 950-956
- Olaptesed pegol (NOX-A12) with bendamustine and rituximab: a phase IIa study in patients with relapsed/refractory chronic lymphocytic leukemia.Haematologica. 2019; 104: 2053-2060
- Impaired endothelial autophagy promotes liver fibrosis by aggravating the oxidative stress response during acute liver injury.J Hepatol. 2019; 70: 458-469
- LncRNA TUG1 regulates autophagy-mediated endothelial-mesenchymal transition of liver sinusoidal endothelial cells by sponging miR-142-3p.Am J Transl Res. 2020; 12: 758-772
- Autophagy-induced p62 accumulation is required for curcumol to regulate KLF5-mediated angiogenesis in liver sinusoidal endothelial cells.Toxicology. 2021; 452152707
- Changes in hepatic venous pressure gradient induced by physical exercise in cirrhosis: results of a pilot randomized open clinical trial.Clin Transl Gastroenterol. 2016; 7: e180
- Liver cirrhosis.Lancet. 2014; 383: 1749-1761
Article info
Publication history
Published online: August 02, 2021
Accepted:
July 12,
2021
Received in revised form:
July 9,
2021
Received:
March 11,
2021
Identification
Copyright
© 2021 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
