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Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a category of hepatic disorders characterized by excessive fat accumulation in the liver, known as steatosis. Over time, accumulated hepatic fat can induce inflammation of the liver (hepatitis). MASLD is among the most prevalent types of chronic liver disease. Obesity and Type 2 diabetes mellitus (T2DM) are frequent etiological factors of MASLD. In the absence of therapy, MASLD can lead to more severe hepatic conditions, which can be life-threatening. MASLD is noteworthy due to its potential progression to MASH and further severe liver impairment, including cirrhosis and hepatocellular carcinoma (HCC), a neoplastic progression. This narrative review examines the distinctive functions of LSECs in regulating immunologic responses, collagenization, and drug-sensitive bioreactivity in healthy livers, MASLD, and metabolic dysfunction-associated steatohepatitis (MASH), as well as in a human primary 3D model. We found that LSECs serve as crucial regulators of immunological equilibrium in the liver by inhibiting disproportionate immunologic activation, concurrently filtering tissue antigens, and engaging with immunologic cells, such as Kupffer cells (KCs) and T lymphocytes. In chronic diseases of the liver, LSECs experience cellular dysfunction, resulting in capillarization (focal to diffuse), loss of fenestrations (fenestrae), and the activation of pro-fibrotic signaling pathways, including transforming growth factor-beta (TGF-\u03b2). Indeed, TGF-\u03b2 is crucial in activating hepatic stellate cells (HSCs), a process that facilitates the progression of liver disease toward fibrosis. In addition to examining the dynamic interplay between LSECs, specifically HSCs, and other liver cells throughout the progression of fatty liver\u2013MASH, we suggest that LSECs may become a potential therapeutic target for modifying immune responses and averting fibrosis in hepatic disorders. The limitations of animal models are also highlighted and discussed.<\/jats:p>","DOI":"10.3390\/ijms26168006","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T11:41:41Z","timestamp":1755603701000},"page":"8006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Liver Sinusoidal Endothelial Cells and Their Regulation of Immunology, Collagenization, and Bioreactivity in Fatty Liver: A Narrative Review"],"prefix":"10.3390","volume":"26","author":[{"given":"Reem J.","family":"Abdulmajeed","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, AB T6G 1B7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2779-7879","authenticated-orcid":false,"given":"Consolato M.","family":"Sergi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Alberta, Edmonton, AB T6G 1B7, Canada"},{"name":"Division of Anatomic Pathology, Children\u2019s Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON K1H 8L1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Puri, M., and Sonawane, S. (2025). Liver Sinusoidal Endothelial Cells in the Regulation of Immune Responses and Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202501.0638.v1"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chen, T., Zhang, H., Shan, W., Zhou, J., and You, Y. (2025). Liver sinusoidal endothelial cells in hepatic fibrosis: Opportunities for future strategies. Biochem. Biophys. Res. Commun., 766.","DOI":"10.1016\/j.bbrc.2025.151881"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1007\/s12072-024-10660-y","article-title":"MAFLD as part of systemic metabolic dysregulation","volume":"18","author":"Zhao","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/j.tem.2024.02.007","article-title":"Current status and future trends of the global burden of MASLD","volume":"35","author":"Miao","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sergi, C.M. (2024). NAFLD (MASLD)\/NASH (MASH): Does It Bother to Label at All? A Comprehensive Narrative Review. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158462"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.dld.2025.01.189","article-title":"Liver sinusoidal endothelial cells: Friend or foe in metabolic dysfunction- associated steatotic liver disease\/metabolic dysfunction-associated steatohepatitis","volume":"57","author":"Dai","year":"2025","journal-title":"Dig. Liver Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s10456-025-09969-5","article-title":"The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: Mechanisms and potential therapies","volume":"28","author":"Mo","year":"2025","journal-title":"Angiogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s00204-024-03886-0","article-title":"Innate immune regulation in inflammation resolution and liver regeneration in drug-induced liver injury","volume":"99","author":"Qian","year":"2025","journal-title":"Arch. Toxicol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tian, S.P., Ge, J.Y., Song, Y.M., Yu, X.Q., Chen, W.H., Chen, Y.Y., Ye, D., and Zheng, Y.W. (2024). A novel efficient strategy to generate liver sinusoidal endothelial cells from human pluripotent stem cells. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64195-1"},{"key":"ref_10","first-page":"101025","article-title":"Advances in nanotechnology for the diagnosis and management of metabolic dysfunction-associated steatotic liver disease","volume":"20","author":"Li","year":"2025","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Arumugam, M.K., Gopal, T., Kandy, R.R.K., Boopathy, L.K., Perumal, S.K., Ganesan, M., Rasineni, K., Donohue, T.M., Osna, N.A., and Kharbanda, K.K. (2023). Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases. Biology, 12.","DOI":"10.3390\/biology12101311"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wu, Q., Yang, Y., Lin, S., Geller, D.A., and Yan, Y. (2025). The microenvironment in the development of MASLD-MASH-HCC and associated therapeutic in MASH-HCC. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1569915"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1007\/s12013-024-01617-x","article-title":"Exosome-mediated Transfer of lncRNA in Liver Associated Diseases; Uncovered Truths","volume":"83","author":"Saleh","year":"2025","journal-title":"Cell Biochem. Biophys."},{"key":"ref_14","first-page":"e0374","article-title":"The role of sinusoidal endothelial cells and TIMP1 in the regulation of fibrosis in a novel human liver 3D NASH model","volume":"8","author":"Julien","year":"2024","journal-title":"Hepatol. Commun."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hardwick, J.P., Song, B.J., Rote, P., Leahy, C., Lee, Y.K., Wolf, A.R., Diegisser, D., and Garcia, V. (2024). The CYP4\/20-HETE\/GPR75 axis in the progression metabolic dysfunction-associated steatosis liver disease (MASLD) to chronic liver disease. Front. Physiol., 15.","DOI":"10.3389\/fphys.2024.1497297"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kremer, K.N., Khammash, H.A., Miranda, A.M., Rutt, L.N., Twardy, S.M., Anton, P.E., Campbell, M.L., Garza-Ortiz, C., Orlicky, D.J., and Pelanda, R. (2024). Liver sinusoidal endothelial cells regulate the balance between hepatic immunosuppression and immunosurveillance. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1497788"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110273","DOI":"10.1016\/j.isci.2024.110273","article-title":"ADAMTS18-fibronectin interaction regulates the morphology of liver sinusoidal endothelial cells","volume":"27","author":"Wang","year":"2024","journal-title":"iScience"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"606","DOI":"10.7150\/ijbs.90781","article-title":"TXNIP in liver sinusoidal endothelial cells ameliorates alcohol-associated liver disease via nitric oxide production","volume":"20","author":"Jung","year":"2024","journal-title":"Int. J. Biol. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1007\/s00018-023-04966-7","article-title":"Liver endothelial cells in NAFLD and transition to NASH and HCC","volume":"80","author":"Velliou","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Wang, X., Guo, Z., Xia, Y., Wang, X., and Wang, Z. (2025). Research Progress on the Immune Function of Liver Sinusoidal Endothelial Cells in Sepsis. Cells, 14.","DOI":"10.3390\/cells14050373"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12951-023-01876-5","article-title":"Remodeling the hepatic fibrotic microenvironment with emerging nanotherapeutics: A comprehensive review","volume":"21","author":"Zhao","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e2411667","DOI":"10.1002\/advs.202411667","article-title":"hESCs-derived Organoids Achieve Liver Zonation Features through LSEC Modulation","volume":"12","author":"Zhang","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3892\/mmr.2024.13164","article-title":"Liver sinusoidal endothelial cells as potential drivers of liver fibrosis (Review)","volume":"29","author":"Gao","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1080\/10408444.2024.2310597","article-title":"Diagnosis, toxicological mechanism, and detoxification for hepatotoxicity induced by pyrrolizidine alkaloids from herbal medicines or other plants","volume":"54","author":"Huang","year":"2024","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s12964-024-01720-9","article-title":"Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease","volume":"22","author":"He","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Borah, D., Blacharczyk, O., Szafranska, K., Czyzynska-Cichon, I., Metwally, S., Szymanowski, K., Hubner, W., Kotlinowski, J., Dobosz, E., and McCourt, P. (2025). Mimicking the Liver Sinusoidal Endothelial Cell Niche In Vitro to Enhance Fenestration in a Genetic Model of Systemic Inflammation. Cells, 14.","DOI":"10.3390\/cells14080621"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Antwi, M.B., Dumitriu, G., Simon-Santamaria, J., Romano, J.S., Li, R., Smedsrod, B., Vik, A., Eskild, W., and Sorensen, K.K. (2023). Liver sinusoidal endothelial cells show reduced scavenger function and downregulation of Fc gamma receptor IIb, yet maintain a preserved fenestration in the Glmpgt\/gt mouse model of slowly progressing liver fibrosis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0293526"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.3748\/wjg.v28.i19.2100","article-title":"Ultrastructural changes in porcine liver sinusoidal endothelial cells of machine perfused liver donated after cardiac death","volume":"28","author":"Bochimoto","year":"2022","journal-title":"World J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.dld.2021.07.006","article-title":"Intercellular crosstalk of liver sinusoidal endothelial cells in liver fibrosis, cirrhosis and hepatocellular carcinoma","volume":"54","author":"Li","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Szafranska, K., Kruse, L.D., Holte, C.F., McCourt, P., and Zapotoczny, B. (2021). The wHole Story About Fenestrations in LSEC. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.735573"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Henriques-Pons, A., Vacani-Martins, N., Dos Santos, C.L.P., and Meuser-Batista, M. (2024). The liver\u2019s dilemma: Sensing real danger in a sea of PAMPs: The (arterial) sinusoidal segment theory. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1503063"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"177730","DOI":"10.1016\/j.ejphar.2025.177730","article-title":"Immune-endothelial cell crosstalk in hepatic endothelial injury of liver fibrotic mice","volume":"1000","author":"Fan","year":"2025","journal-title":"Eur. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e70585","DOI":"10.1111\/jcmm.70585","article-title":"Disruption of Hepatic Sinusoidal Homeostasis Leads to Hepatopulmonary Syndrome","volume":"29","author":"Chen","year":"2025","journal-title":"J. Cell. Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kouroumalis, E., Tsomidis, I., and Voumvouraki, A. (2025). HFE-Related Hemochromatosis May Be a Primary Kupffer Cell Disease. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030683"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wu, D., Zhu, H., and Wang, H. (2021). Extracellular Vesicles in Non-alcoholic Fatty Liver Disease and Alcoholic Liver Disease. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.707429"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Feng, H., Ou, B., Dong, W., and Thasler, W.E. (2018). Preparation and Culture of Human Liver Resident Immune Cells. Curr. Protoc. Cell Biol., 80.","DOI":"10.1002\/cpcb.50"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.jconrel.2025.01.036","article-title":"Targeted delivery of polymeric NO-donor micelles to hepatic stellate cells for restoration of liver function and inhibition of hepatic fibrosis","volume":"379","author":"Yang","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1080\/15548627.2023.2254191","article-title":"Dysfunction of autophagy in high-fat diet-induced non-alcoholic fatty liver disease","volume":"20","author":"Ren","year":"2024","journal-title":"Autophagy"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Nesci, A., Ruggieri, V., Manilla, V., Spinelli, I., Santoro, L., Di Giorgio, A., Santoliquido, A., and Ponziani, F.R. (2024). Endothelial Dysfunction and Liver Cirrhosis: Unraveling of a Complex Relationship. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms252312859"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Guo, Q., Furuta, K., Islam, S., Caporarello, N., Kostallari, E., Dielis, K., Tschumperlin, D.J., Hirsova, P., and Ibrahim, S.H. (2022). Liver sinusoidal endothelial cell expressed vascular cell adhesion molecule 1 promotes liver fibrosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.983255"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1021\/acsnano.2c12420","article-title":"Use of a Liver-Targeting Immune-Tolerogenic mRNA Lipid Nanoparticle Platform to Treat Peanut-Induced Anaphylaxis by Single- and Multiple-Epitope Nucleotide Sequence Delivery","volume":"17","author":"Xu","year":"2023","journal-title":"ACS Nano"},{"key":"ref_42","first-page":"e0700","article-title":"miR-27b-3p modulates liver sinusoidal endothelium dedifferentiation in chronic liver disease","volume":"9","author":"Hunt","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.toxlet.2024.08.011","article-title":"beta-arrestin2 promotes angiogenesis of liver sinusoidal endothelial cells through the VEGF\/VEGFR2 pathway to aggravate cirrhosis","volume":"401","author":"Gao","year":"2024","journal-title":"Toxicol. Lett."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Vasuri, F., Germinario, G., Ciavarella, C., Carroli, M., Motta, I., Valente, S., Cescon, M., D\u2019Errico, A., Pasquinelli, G., and Ravaioli, M. (2022). Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion. Biology, 11.","DOI":"10.3390\/biology11091329"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1021\/acsnano.0c09206","article-title":"Antigen- and Epitope-Delivering Nanoparticles Targeting Liver Induce Comparable Immunotolerance in Allergic Airway Disease and Anaphylaxis as Nanoparticle-Delivering Pharmaceuticals","volume":"15","author":"Liu","year":"2021","journal-title":"ACS Nano"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Lei, H., Reinke, P., Volk, H.D., Lv, Y., and Wu, R. (2019). Mechanisms of Immune Tolerance in Liver Transplantation-Crosstalk Between Alloreactive T Cells and Liver Cells With Therapeutic Prospects. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02667"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"4778","DOI":"10.1021\/acsnano.9b01444","article-title":"Use of Polymeric Nanoparticle Platform Targeting the Liver To Induce Treg-Mediated Antigen-Specific Immune Tolerance in a Pulmonary Allergen Sensitization Model","volume":"13","author":"Liu","year":"2019","journal-title":"ACS Nano"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"van Son, K.C., Verschuren, L., Hanemaaijer, R., Reeves, H., Takkenberg, R.B., Drenth, J.P.H., Tushuizen, M.E., and Holleboom, A.G. (2023). Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease. Cancers, 15.","DOI":"10.3390\/cancers15041308"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yu, M., Zheng, C., Li, X., Ji, X., Hu, X., Wang, X., and Zhang, J. (2025). Neutrophil extracellular traps-induced pyroptosis of liver sinusoidal endothelial cells exacerbates intrahepatic coagulation in cholestatic mice. Biochim. Biophys. Acta Mol. Basis Dis., 1871.","DOI":"10.1016\/j.bbadis.2025.167700"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Heldens, A., Casteleyn, C., Onghena, L., Antwi, M., Neyt, S., Descamps, B., Vanhove, C., Verhelst, X., Raevens, S., and Van Vlierberghe, H. (2025). The pan-PPAR agonist lanifibranor reduces portal pressure independent of fibrosis reduction through the splanchnic vasculature. Biomed. Pharmacother., 183.","DOI":"10.1016\/j.biopha.2025.117826"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Czyzynska-Cichon, I., Kotlinowski, J., Blacharczyk, O., Giergiel, M., Szymanowski, K., Metwally, S., Wojnar-Lason, K., Dobosz, E., Koziel, J., and Lekka, M. (2024). Early and late phases of liver sinusoidal endothelial cell (LSEC) defenestration in mouse model of systemic inflammation. Cell. Mol. Biol. Lett., 29.","DOI":"10.1186\/s11658-024-00655-w"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.pathol.2020.07.018","article-title":"Electron microscopic observations in perfusion-fixed human non-alcoholic fatty liver disease biopsies","volume":"53","author":"Verhaegh","year":"2021","journal-title":"Pathology"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Baiocchini, A., Del Nonno, F., Taibi, C., Visco-Comandini, U., D\u2019Offizi, G., Piacentini, M., and Falasca, L. (2019). Liver sinusoidal endothelial cells (LSECs) modifications in patients with chronic hepatitis C. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-45114-1"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4517","DOI":"10.1038\/s41467-025-59885-x","article-title":"Nucleic acid spheres for treating capillarisation of liver sinusoidal endothelial cells in liver fibrosis","volume":"16","author":"Liu","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.celrep.2014.07.008","article-title":"IL-6 trans-signaling-dependent rapid development of cytotoxic CD8+ T cell function","volume":"8","author":"Bottcher","year":"2014","journal-title":"Cell Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4185","DOI":"10.4049\/jimmunol.1203091","article-title":"Liver sinusoidal endothelial cell lectin inhibits CTL-dependent virus clearance in mouse models of viral hepatitis","volume":"190","author":"Liu","year":"2013","journal-title":"J. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12950-024-00387-w","article-title":"Microcirculatory disturbance in acute liver injury is triggered by IFNgamma-CD40 axis","volume":"21","author":"Kurokawa","year":"2024","journal-title":"J. Inflamm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3350\/cmh.2024.0022","article-title":"Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis","volume":"30","author":"Qu","year":"2024","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_59","first-page":"452","article-title":"Update in lean metabolic dysfunction-associated steatotic liver disease","volume":"16","author":"Chotiprasidhi","year":"2024","journal-title":"World J. Hepatol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"111648","DOI":"10.1016\/j.diabres.2024.111648","article-title":"Epidemiology of NAFLD\u2014Focus on diabetes","volume":"210","author":"Younossi","year":"2024","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.livres.2024.03.002","article-title":"Targeting nuclear receptors for NASH\/MASH: From bench to bedside","volume":"8","author":"Sinha","year":"2024","journal-title":"Liver Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jhep.2023.11.004","article-title":"Global survey of stigma among physicians and patients with nonalcoholic fatty liver disease","volume":"80","author":"Younossi","year":"2024","journal-title":"J. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"101133","DOI":"10.1016\/j.aohep.2023.101133","article-title":"A multisociety Delphi consensus statement on new fatty liver disease nomenclature","volume":"29","author":"Rinella","year":"2024","journal-title":"Ann. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"20420188241227766","DOI":"10.1177\/20420188241227766","article-title":"Liver Biopsy Handling of Metabolic-Associated Fatty Liver Disease (MAFLD): The Children\u2019s Hospital of Eastern Ontario grossing protocol","volume":"15","author":"Sergi","year":"2024","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bhandari, S., Larsen, A.K., McCourt, P., Smedsrod, B., and Sorensen, K.K. (2021). The Scavenger Function of Liver Sinusoidal Endothelial Cells in Health and Disease. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.757469"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.pcd.2024.01.004","article-title":"Association of metabolic syndrome components and NAFLD with quality of life: Insights from a cross-sectional study","volume":"18","author":"Leite","year":"2024","journal-title":"Prim. Care Diabetes"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Susak, F., Vrsaljko, N., Vince, A., and Papic, N. (2023). TGF Beta as a Prognostic Biomarker of COVID-19 Severity in Patients with NAFLD-A Prospective Case-Control Study. Microorganisms, 11.","DOI":"10.3390\/microorganisms11061571"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Trampuz, S.R., van Riet, S., Nordling, A., and Ingelman-Sundberg, M. (2023). The Role of CTGF in Liver Fibrosis Induced in 3D Human Liver Spheroids. Cells, 12.","DOI":"10.3390\/cells12020302"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1111\/jcmm.17698","article-title":"TGFbeta(1) priming enhances CXCR3-mediated mesenchymal stromal cell engraftment to the liver and enhances anti-inflammatory efficacy","volume":"27","author":"Garg","year":"2023","journal-title":"J. Cell. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1007\/s11655-021-3304-y","article-title":"Amygdalin Ameliorates Liver Fibrosis through Inhibiting Activation of TGF-beta\/Smad Signaling","volume":"29","author":"Xiao","year":"2023","journal-title":"Chin. J. Integr. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12072-023-10606-w","article-title":"Autophagy and extracellular vesicles in the liver endothelium: Friends or foes?","volume":"18","author":"Biquard","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"114629","DOI":"10.1016\/j.celrep.2024.114629","article-title":"Human liver sinusoidal endothelial cells support the development of functional human pluripotent stem cell-derived Kupffer cells","volume":"43","author":"Kent","year":"2024","journal-title":"Cell Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Lafoz, E., Ruart, M., Anton, A., Oncins, A., and Hernandez-Gea, V. (2020). The Endothelium as a Driver of Liver Fibrosis and Regeneration. Cells, 9.","DOI":"10.3390\/cells9040929"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1097\/MPG.0b013e31824b6391","article-title":"Angiogenic remodeling in pediatric EoE is associated with increased levels of VEGF-A, angiogenin, IL-8, and activation of the TNF-alpha-NFkappaB pathway","volume":"55","author":"Persad","year":"2012","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Sergi, C. (2019). EPAS 1, congenital heart disease, and high altitude: Disclosures by genetics, bioinformatics, and experimental embryology. Biosci. Rep., 39.","DOI":"10.1042\/BSR20182197"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"77591","DOI":"10.18632\/oncotarget.12728","article-title":"Nuclear FOXO3 predicts adverse clinical outcome and promotes tumor angiogenesis in neuroblastoma","volume":"7","author":"Hagenbuchner","year":"2016","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.2337\/db22-0933","article-title":"Trajectories of Liver Fibrosis and Gene Expression Profiles in Nonalcoholic Fatty Liver Disease Associated with Diabetes","volume":"72","author":"Sako","year":"2023","journal-title":"Diabetes"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e22125","DOI":"10.1096\/fj.202101426R","article-title":"Endothelial dysfunction in pathological processes of chronic liver disease during aging","volume":"36","author":"Wan","year":"2022","journal-title":"FASEB J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"113869","DOI":"10.1016\/j.addr.2021.113869","article-title":"Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis","volume":"176","author":"Kumar","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molimm.2019.09.009","article-title":"Contribution of endothelial cell and macrophage activation in the alterations induced by the venom of Micrurus tener tener in C57BL\/6 mice","volume":"116","author":"Salazar","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Benedicto, A., Herrero, A., Romayor, I., Marquez, J., Smedsrod, B., Olaso, E., and Arteta, B. (2019). Liver sinusoidal endothelial cell ICAM-1 mediated tumor\/endothelial crosstalk drives the development of liver metastasis by initiating inflammatory and angiogenic responses. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-49473-7"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1111\/liv.12849","article-title":"Infusion of endothelial progenitor cells ameliorates liver injury in mice after haematopoietic stem cell transplantation","volume":"35","author":"Qiao","year":"2015","journal-title":"Liver Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"7997","DOI":"10.3390\/cimb46080473","article-title":"Transcriptome Analyses of Liver Sinusoidal Endothelial Cells Reveal a Consistent List of Candidate Genes Associated with Endothelial Dysfunction and the Fibrosis Progression","volume":"46","author":"Li","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"108372","DOI":"10.1016\/j.pharmthera.2023.108372","article-title":"Endotheliopathy in the metabolic syndrome: Mechanisms and clinical implications","volume":"244","author":"Furuta","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"100684","DOI":"10.1016\/j.jhepr.2023.100684","article-title":"High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis","volume":"5","author":"Schmalz","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"100524","DOI":"10.1016\/j.jhepr.2022.100524","article-title":"Understanding the cellular interactome of non-alcoholic fatty liver disease","volume":"4","author":"Wallace","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s13020-024-01038-1","article-title":"Si-Wu-Tang improves liver fibrosis by restoring liver sinusoidal endothelial cell functionality and reducing communication with hepatic stellate cells","volume":"19","author":"Wang","year":"2024","journal-title":"Chin. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e2400643","DOI":"10.1002\/smll.202400643","article-title":"In Vivo Endothelial Cell Gene Silencing by siRNA-LNPs Tuned with Lipoamino Bundle Chemical and Ligand Targeting","volume":"20","author":"Yazdi","year":"2024","journal-title":"Small"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Bhandari, S., Kyrrestad, I., Simon-Santamaria, J., Li, R., Szafranska, K.J., Dumitriu, G., Romano, J.S., Smedsrod, B., and Sorensen, K.K. (2024). Mouse liver sinusoidal endothelial cell responses to the glucocorticoid receptor agonist dexamethasone. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1377136"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"101023","DOI":"10.1016\/j.jhepr.2024.101023","article-title":"Liver specification of human iPSC-derived endothelial cells transplanted into mouse liver","volume":"6","author":"Yap","year":"2024","journal-title":"JHEP Rep."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1002\/hep.32332","article-title":"Notch-triggered maladaptation of liver sinusoidal endothelium aggravates nonalcoholic steatohepatitis through endothelial nitric oxide synthase","volume":"76","author":"Fang","year":"2022","journal-title":"Hepatology"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Casey, L.M., Hughes, K.R., Saunders, M.N., Miller, S.D., Pearson, R.M., and Shea, L.D. (2022). Mechanistic contributions of Kupffer cells and liver sinusoidal endothelial cells in nanoparticle-induced antigen-specific immune tolerance. Biomaterials, 283.","DOI":"10.1016\/j.biomaterials.2022.121457"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Yu, Z., Guo, J., Liu, Y., Wang, M., Liu, Z., Gao, Y., and Huang, L. (2022). Nano delivery of simvastatin targets liver sinusoidal endothelial cells to remodel tumor microenvironment for hepatocellular carcinoma. J. Nanobiotechnol., 20.","DOI":"10.1186\/s12951-021-01205-8"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Tolksdorf, F., Mikulec, J., Geers, B., Endig, J., Sprezyna, P., Heukamp, L.C., Knolle, P.A., Kolanus, W., and Diehl, L. (2018). The PDL1-inducible GTPase Arl4d controls T effector function by limiting IL-2 production. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-34522-4"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"100251","DOI":"10.1016\/j.jhepr.2021.100251","article-title":"New insights on the role of vascular endothelial growth factor in biliary pathophysiology","volume":"3","author":"Mariotti","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Auvinen, K., Lokka, E., Mokkala, E., Jappinen, N., Tyystjarvi, S., Saine, H., Peurla, M., Shetty, S., Elima, K., and Rantakari, P. (2019). Fenestral diaphragms and PLVAP associations in liver sinusoidal endothelial cells are developmentally regulated. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-52068-x"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"7219","DOI":"10.7150\/thno.99926","article-title":"Gut microbiota depletion and FXR inhibition exacerbates zonal hepatotoxicity of sunitinib","volume":"14","author":"Zhao","year":"2024","journal-title":"Theranostics"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/15548627.2021.1895658","article-title":"The menage a trois of autophagy, lipid droplets and liver disease","volume":"18","author":"Hunter","year":"2022","journal-title":"Autophagy"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Zapotoczny, B., Szafranska, K., Lekka, M., Ahluwalia, B.S., and McCourt, P. (2022). Tuning of Liver Sieve: The Interplay between Actin and Myosin Regulatory Light Chain Regulates Fenestration Size and Number in Murine Liver Sinusoidal Endothelial Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179850"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1111\/tra.12700","article-title":"Actin-spectrin scaffold supports open fenestrae in liver sinusoidal endothelial cells","volume":"20","author":"Zapotoczny","year":"2019","journal-title":"Traffic"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1002\/hep.30232","article-title":"Tracking Fenestrae Dynamics in Live Murine Liver Sinusoidal Endothelial Cells","volume":"69","author":"Zapotoczny","year":"2019","journal-title":"Hepatology"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Zapotoczny, B., Szafranska, K., Owczarczyk, K., Kus, E., Chlopicki, S., and Szymonski, M. (2017). Atomic Force Microscopy Reveals the Dynamic Morphology of Fenestrations in Live Liver Sinusoidal Endothelial Cells. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-08555-0"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e2610","DOI":"10.1002\/jmr.2610","article-title":"Morphology and force probing of primary murine liver sinusoidal endothelial cells","volume":"30","author":"Zapotoczny","year":"2017","journal-title":"J. Mol. Recognit."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Targosz-Korecka, M., Jaglarz, M., Malek-Zietek, K.E., Gregorius, A., Zakrzewska, A., Sitek, B., Rajfur, Z., Chlopicki, S., and Szymonski, M. (2017). AFM-based detection of glycocalyx degradation and endothelial stiffening in the db\/db mouse model of diabetes. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-16179-7"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s12551-020-00699-0","article-title":"Biophysical nanocharacterization of liver sinusoidal endothelial cells through atomic force microscopy","volume":"12","author":"Zapotoczny","year":"2020","journal-title":"Biophys. Rev."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"18867","DOI":"10.1039\/C7NR05851A","article-title":"Robust oil-core nanocapsules with hyaluronate-based shells as promising nanovehicles for lipophilic compounds","volume":"9","author":"Szafraniec","year":"2017","journal-title":"Nanoscale"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.micron.2017.06.005","article-title":"Quantification of fenestrations in liver sinusoidal endothelial cells by atomic force microscopy","volume":"101","author":"Zapotoczny","year":"2017","journal-title":"Micron"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8006\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:30:54Z","timestamp":1760034654000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,19]]},"references-count":107,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26168006"],"URL":"https:\/\/doi.org\/10.3390\/ijms26168006","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,19]]}}}