Skip to main content
Top
Published in: Angiogenesis 2/2021

Open Access 01-05-2021 | Review Paper

Angiodiversity and organotypic functions of sinusoidal endothelial cells

Authors: Philipp-Sebastian Koch, Ki Hong Lee, Sergij Goerdt, Hellmut G. Augustin

Published in: Angiogenesis | Issue 2/2021

Login to get access

Abstract

‘Angiodiversity’ refers to the structural and functional heterogeneity of endothelial cells (EC) along the segments of the vascular tree and especially within the microvascular beds of different organs. Organotypically differentiated EC ranging from continuous, barrier-forming endothelium to discontinuous, fenestrated endothelium perform organ-specific functions such as the maintenance of the tightly sealed blood–brain barrier or the clearance of macromolecular waste products from the peripheral blood by liver EC-expressed scavenger receptors. The microvascular bed of the liver, composed of discontinuous, fenestrated liver sinusoidal endothelial cells (LSEC), is a prime example of organ-specific angiodiversity. Anatomy and development of LSEC have been extensively studied by electron microscopy as well as linage-tracing experiments. Recent advances in cell isolation and bulk transcriptomics or single-cell RNA sequencing techniques allowed the identification of distinct LSEC molecular programs and have led to the identification of LSEC subpopulations. LSEC execute homeostatic functions such as fine tuning the vascular tone, clearing noxious substances from the circulation, and modulating immunoregulatory mechanisms. In recent years, the identification and functional analysis of LSEC-derived angiocrine signals, which control liver homeostasis and disease pathogenesis in an instructive manner, marks a major change of paradigm in the understanding of liver function in health and disease. This review summarizes recent advances in the understanding of liver vascular angiodiversity and the functional consequences resulting thereof.
Literature
4.
go back to reference Nolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, Ding BS, Schachterle W, Liu Y, Rosenwaks Z, Butler JM, Xiang J, Rafii A, Shido K, Rabbany SY, Elemento O, Rafii S (2013) Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell 26(2):204–219. https://doi.org/10.1016/j.devcel.2013.06.017CrossRefPubMed Nolan DJ, Ginsberg M, Israely E, Palikuqi B, Poulos MG, James D, Ding BS, Schachterle W, Liu Y, Rosenwaks Z, Butler JM, Xiang J, Rafii A, Shido K, Rabbany SY, Elemento O, Rafii S (2013) Molecular signatures of tissue-specific microvascular endothelial cell heterogeneity in organ maintenance and regeneration. Dev Cell 26(2):204–219. https://​doi.​org/​10.​1016/​j.​devcel.​2013.​06.​017CrossRefPubMed
12.
go back to reference Planas-Paz L, Orsini V, Boulter L, Calabrese D, Pikiolek M, Nigsch F, Xie Y, Roma G, Donovan A, Marti P, Beckmann N, Dill MT, Carbone W, Bergling S, Isken A, Mueller M, Kinzel B, Yang Y, Mao X, Nicholson TB, Zamponi R, Capodieci P, Valdez R, Rivera D, Loew A, Ukomadu C, Terracciano LM, Bouwmeester T, Cong F, Heim MH, Forbes SJ, Ruffner H, Tchorz JS (2016) The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size. Nat Cell Biol 18(5):467–479. https://doi.org/10.1038/ncb3337CrossRefPubMed Planas-Paz L, Orsini V, Boulter L, Calabrese D, Pikiolek M, Nigsch F, Xie Y, Roma G, Donovan A, Marti P, Beckmann N, Dill MT, Carbone W, Bergling S, Isken A, Mueller M, Kinzel B, Yang Y, Mao X, Nicholson TB, Zamponi R, Capodieci P, Valdez R, Rivera D, Loew A, Ukomadu C, Terracciano LM, Bouwmeester T, Cong F, Heim MH, Forbes SJ, Ruffner H, Tchorz JS (2016) The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size. Nat Cell Biol 18(5):467–479. https://​doi.​org/​10.​1038/​ncb3337CrossRefPubMed
15.
19.
go back to reference Wakabayashi T, Naito H, Suehiro JI, Lin Y, Kawaji H, Iba T, Kouno T, Ishikawa-Kato S, Furuno M, Takara K, Muramatsu F, Weizhen J, Kidoya H, Ishihara K, Hayashizaki Y, Nishida K, Yoder MC, Takakura N (2018) CD157 marks tissue-resident endothelial stem cells with homeostatic and regenerative properties. Cell Stem Cell 22(3):384–397. https://doi.org/10.1016/j.stem.2018.01.010CrossRefPubMed Wakabayashi T, Naito H, Suehiro JI, Lin Y, Kawaji H, Iba T, Kouno T, Ishikawa-Kato S, Furuno M, Takara K, Muramatsu F, Weizhen J, Kidoya H, Ishihara K, Hayashizaki Y, Nishida K, Yoder MC, Takakura N (2018) CD157 marks tissue-resident endothelial stem cells with homeostatic and regenerative properties. Cell Stem Cell 22(3):384–397. https://​doi.​org/​10.​1016/​j.​stem.​2018.​01.​010CrossRefPubMed
21.
go back to reference Bonnardel J, T’Jonck W, Gaublomme D, Browaeys R, Scott CL, Martens L, Vanneste B, De Prijck S, Nedospasov SA, Kremer A, Van Hamme E, Borghgraef P, Toussaint W, De Bleser P, Mannaerts I, Beschin A, van Grunsven LA, Lambrecht BN, Taghon T, Lippens S, Elewaut D, Saeys Y, Guilliams M (2019) Stellate cells, hepatocytes, and endothelial cells imprint the kupffer cell identity on monocytes colonizing the liver macrophage niche. Immunity 51(4):638–654. https://doi.org/10.1016/j.immuni.2019.08.017CrossRefPubMedPubMedCentral Bonnardel J, T’Jonck W, Gaublomme D, Browaeys R, Scott CL, Martens L, Vanneste B, De Prijck S, Nedospasov SA, Kremer A, Van Hamme E, Borghgraef P, Toussaint W, De Bleser P, Mannaerts I, Beschin A, van Grunsven LA, Lambrecht BN, Taghon T, Lippens S, Elewaut D, Saeys Y, Guilliams M (2019) Stellate cells, hepatocytes, and endothelial cells imprint the kupffer cell identity on monocytes colonizing the liver macrophage niche. Immunity 51(4):638–654. https://​doi.​org/​10.​1016/​j.​immuni.​2019.​08.​017CrossRefPubMedPubMedCentral
29.
go back to reference Braet F, De Zanger R, Baekeland M, Crabbe E, Van Der Smissen P, Wisse E (1995) Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells. Hepatology 21(1):180–189PubMed Braet F, De Zanger R, Baekeland M, Crabbe E, Van Der Smissen P, Wisse E (1995) Structure and dynamics of the fenestrae-associated cytoskeleton of rat liver sinusoidal endothelial cells. Hepatology 21(1):180–189PubMed
32.
go back to reference Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G (1996) Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood 87(11):4568–4580CrossRefPubMed Couvelard A, Scoazec JY, Dauge MC, Bringuier AF, Potet F, Feldmann G (1996) Structural and functional differentiation of sinusoidal endothelial cells during liver organogenesis in humans. Blood 87(11):4568–4580CrossRefPubMed
35.
36.
go back to reference Geraud C, Koch PS, Zierow J, Klapproth K, Busch K, Olsavszky V, Leibing T, Demory A, Ulbrich F, Diett M, Singh S, Sticht C, Breitkopf-Heinlein K, Richter K, Karppinen SM, Pihlajaniemi T, Arnold B, Rodewald HR, Augustin HG, Schledzewski K, Goerdt S (2017) GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis. J Clin Invest 127(3):1099–1114. https://doi.org/10.1172/JCI90086CrossRefPubMedPubMedCentral Geraud C, Koch PS, Zierow J, Klapproth K, Busch K, Olsavszky V, Leibing T, Demory A, Ulbrich F, Diett M, Singh S, Sticht C, Breitkopf-Heinlein K, Richter K, Karppinen SM, Pihlajaniemi T, Arnold B, Rodewald HR, Augustin HG, Schledzewski K, Goerdt S (2017) GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis. J Clin Invest 127(3):1099–1114. https://​doi.​org/​10.​1172/​JCI90086CrossRefPubMedPubMedCentral
51.
go back to reference Arai T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Iesato Y, Koyama T, Yoshizawa T, Uetake R, Yamauchi A, Yang L, Kawate H, Ogawa S, Kobayashi A, Miyagawa S, Shindo T (2011) Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling. Peptides 32(9):1855–1865. https://doi.org/10.1016/j.peptides.2011.07.005CrossRefPubMed Arai T, Sakurai T, Kamiyoshi A, Ichikawa-Shindo Y, Iinuma N, Iesato Y, Koyama T, Yoshizawa T, Uetake R, Yamauchi A, Yang L, Kawate H, Ogawa S, Kobayashi A, Miyagawa S, Shindo T (2011) Induction of LYVE-1/stabilin-2-positive liver sinusoidal endothelial-like cells from embryoid bodies by modulation of adrenomedullin-RAMP2 signaling. Peptides 32(9):1855–1865. https://​doi.​org/​10.​1016/​j.​peptides.​2011.​07.​005CrossRefPubMed
58.
go back to reference Geraud C, Schledzewski K, Demory A, Klein D, Kaus M, Peyre F, Sticht C, Evdokimov K, Lu S, Schmieder A, Goerdt S (2010) Liver sinusoidal endothelium: a microenvironment-dependent differentiation program in rat including the novel junctional protein liver endothelial differentiation-associated protein-1. Hepatology 52(1):313–326. https://doi.org/10.1002/hep.23618CrossRefPubMed Geraud C, Schledzewski K, Demory A, Klein D, Kaus M, Peyre F, Sticht C, Evdokimov K, Lu S, Schmieder A, Goerdt S (2010) Liver sinusoidal endothelium: a microenvironment-dependent differentiation program in rat including the novel junctional protein liver endothelial differentiation-associated protein-1. Hepatology 52(1):313–326. https://​doi.​org/​10.​1002/​hep.​23618CrossRefPubMed
59.
go back to reference Olsavszky V, Ulbrich F, Singh S, Diett M, Sticht C, Schmid CD, Zierow J, Wohlfeil SA, Schledzewski K, Dooley S, Gaitantzi H, Breitkopf-Heinlein K, Geraud C, Goerdt S, Koch PS (2017) GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells. Gene 627:491–499. https://doi.org/10.1016/j.gene.2017.06.051CrossRefPubMed Olsavszky V, Ulbrich F, Singh S, Diett M, Sticht C, Schmid CD, Zierow J, Wohlfeil SA, Schledzewski K, Dooley S, Gaitantzi H, Breitkopf-Heinlein K, Geraud C, Goerdt S, Koch PS (2017) GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells. Gene 627:491–499. https://​doi.​org/​10.​1016/​j.​gene.​2017.​06.​051CrossRefPubMed
60.
go back to reference Wohlfeil SA, Hafele V, Dietsch B, Schledzewski K, Winkler M, Zierow J, Leibing T, Mohammadi MM, Heineke J, Sticht C, Olsavszky V, Koch PS, Geraud C, Goerdt S (2019) Hepatic endothelial Notch activation protects against liver metastasis by regulating endothelial-tumor cell adhesion independent of angiocrine signaling. Cancer Res 79(3):598–610. https://doi.org/10.1158/0008-5472.CAN-18-1752CrossRefPubMed Wohlfeil SA, Hafele V, Dietsch B, Schledzewski K, Winkler M, Zierow J, Leibing T, Mohammadi MM, Heineke J, Sticht C, Olsavszky V, Koch PS, Geraud C, Goerdt S (2019) Hepatic endothelial Notch activation protects against liver metastasis by regulating endothelial-tumor cell adhesion independent of angiocrine signaling. Cancer Res 79(3):598–610. https://​doi.​org/​10.​1158/​0008-5472.​CAN-18-1752CrossRefPubMed
61.
go back to reference Winkler M, Staniczek T, Kurschner SW, Schmid CD, Schonhaber H, Cordero J, Kessler L, Mathes A, Sticht C, Nessling M, Uvarovskii A, Anders S, Zhang XJ, von Figura G, Hartmann D, Mogler C, Dobreva G, Schledzewski K, Geraud C, Koch PS, Goerdt S (2021) Endothelial GATA4 controls liver fibrosis and regeneration by preventing a pathogenic switch in angiocrine signaling. J Hepatol 74(2):380–393. https://doi.org/10.1016/j.jhep.2020.08.033CrossRefPubMed Winkler M, Staniczek T, Kurschner SW, Schmid CD, Schonhaber H, Cordero J, Kessler L, Mathes A, Sticht C, Nessling M, Uvarovskii A, Anders S, Zhang XJ, von Figura G, Hartmann D, Mogler C, Dobreva G, Schledzewski K, Geraud C, Koch PS, Goerdt S (2021) Endothelial GATA4 controls liver fibrosis and regeneration by preventing a pathogenic switch in angiocrine signaling. J Hepatol 74(2):380–393. https://​doi.​org/​10.​1016/​j.​jhep.​2020.​08.​033CrossRefPubMed
62.
go back to reference Kalucka J, de Rooij L, Goveia J, Rohlenova K, Dumas SJ, Meta E, Conchinha NV, Taverna F, Teuwen LA, Veys K, Garcia-Caballero M, Khan S, Geldhof V, Sokol L, Chen R, Treps L, Borri M, de Zeeuw P, Dubois C, Karakach TK, Falkenberg KD, Parys M, Yin X, Vinckier S, Du Y, Fenton RA, Schoonjans L, Dewerchin M, Eelen G, Thienpont B, Lin L, Bolund L, Li X, Luo Y, Carmeliet P (2020) Single-cell transcriptome atlas of murine endothelial cells. Cell 180(4):764–779. https://doi.org/10.1016/j.cell.2020.01.015CrossRefPubMed Kalucka J, de Rooij L, Goveia J, Rohlenova K, Dumas SJ, Meta E, Conchinha NV, Taverna F, Teuwen LA, Veys K, Garcia-Caballero M, Khan S, Geldhof V, Sokol L, Chen R, Treps L, Borri M, de Zeeuw P, Dubois C, Karakach TK, Falkenberg KD, Parys M, Yin X, Vinckier S, Du Y, Fenton RA, Schoonjans L, Dewerchin M, Eelen G, Thienpont B, Lin L, Bolund L, Li X, Luo Y, Carmeliet P (2020) Single-cell transcriptome atlas of murine endothelial cells. Cell 180(4):764–779. https://​doi.​org/​10.​1016/​j.​cell.​2020.​01.​015CrossRefPubMed
67.
go back to reference Lorenz L, Axnick J, Buschmann T, Henning C, Urner S, Fang S, Nurmi H, Eichhorst N, Holtmeier R, Bodis K, Hwang JH, Mussig K, Eberhard D, Stypmann J, Kuss O, Roden M, Alitalo K, Haussinger D, Lammert E (2018) Mechanosensing by beta1 integrin induces angiocrine signals for liver growth and survival. Nature 562(7725):128–132. https://doi.org/10.1038/s41586-018-0522-3CrossRefPubMed Lorenz L, Axnick J, Buschmann T, Henning C, Urner S, Fang S, Nurmi H, Eichhorst N, Holtmeier R, Bodis K, Hwang JH, Mussig K, Eberhard D, Stypmann J, Kuss O, Roden M, Alitalo K, Haussinger D, Lammert E (2018) Mechanosensing by beta1 integrin induces angiocrine signals for liver growth and survival. Nature 562(7725):128–132. https://​doi.​org/​10.​1038/​s41586-018-0522-3CrossRefPubMed
70.
go back to reference Omori S, Wang TW, Johmura Y, Kanai T, Nakano Y, Kido T, Susaki EA, Nakajima T, Shichino S, Ueha S, Ozawa M, Yokote K, Kumamoto S, Nishiyama A, Sakamoto T, Yamaguchi K, Hatakeyama S, Shimizu E, Katayama K, Yamada Y, Yamazaki S, Iwasaki K, Miyoshi C, Funato H, Yanagisawa M, Ueno H, Imoto S, Furukawa Y, Yoshida N, Matsushima K, Ueda HR, Miyajima A, Nakanishi M (2020) Generation of a p16 reporter mouse and its use to characterize and target p16(high) cells in vivo. Cell Metab 32(5):814–828. https://doi.org/10.1016/j.cmet.2020.09.006CrossRefPubMed Omori S, Wang TW, Johmura Y, Kanai T, Nakano Y, Kido T, Susaki EA, Nakajima T, Shichino S, Ueha S, Ozawa M, Yokote K, Kumamoto S, Nishiyama A, Sakamoto T, Yamaguchi K, Hatakeyama S, Shimizu E, Katayama K, Yamada Y, Yamazaki S, Iwasaki K, Miyoshi C, Funato H, Yanagisawa M, Ueno H, Imoto S, Furukawa Y, Yoshida N, Matsushima K, Ueda HR, Miyajima A, Nakanishi M (2020) Generation of a p16 reporter mouse and its use to characterize and target p16(high) cells in vivo. Cell Metab 32(5):814–828. https://​doi.​org/​10.​1016/​j.​cmet.​2020.​09.​006CrossRefPubMed
71.
go back to reference Hilscher MB, Sehrawat T, Arab JP, Zeng Z, Gao J, Liu M, Kostallari E, Gao Y, Simonetto DA, Yaqoob U, Cao S, Revzin A, Beyder A, Wang RA, Kamath PS, Kubes P, Shah VH (2019) Mechanical stretch increases expression of CXCL1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension. Gastroenterology 157(1):193–209. https://doi.org/10.1053/j.gastro.2019.03.013CrossRefPubMed Hilscher MB, Sehrawat T, Arab JP, Zeng Z, Gao J, Liu M, Kostallari E, Gao Y, Simonetto DA, Yaqoob U, Cao S, Revzin A, Beyder A, Wang RA, Kamath PS, Kubes P, Shah VH (2019) Mechanical stretch increases expression of CXCL1 in liver sinusoidal endothelial cells to recruit neutrophils, generate sinusoidal microthombi, and promote portal hypertension. Gastroenterology 157(1):193–209. https://​doi.​org/​10.​1053/​j.​gastro.​2019.​03.​013CrossRefPubMed
73.
go back to reference Jackel S, Kiouptsi K, Lillich M, Hendrikx T, Khandagale A, Kollar B, Hormann N, Reiss C, Subramaniam S, Wilms E, Ebner K, Bruhl MV, Rausch P, Baines JF, Haberichter S, Lammle B, Binder CJ, Jurk K, Ruggeri ZM, Massberg S, Walter U, Ruf W, Reinhardt C (2017) Gut microbiota regulate hepatic von Willebrand factor synthesis and arterial thrombus formation via Toll-like receptor-2. Blood 130(4):542–553. https://doi.org/10.1182/blood-2016-11-754416CrossRefPubMed Jackel S, Kiouptsi K, Lillich M, Hendrikx T, Khandagale A, Kollar B, Hormann N, Reiss C, Subramaniam S, Wilms E, Ebner K, Bruhl MV, Rausch P, Baines JF, Haberichter S, Lammle B, Binder CJ, Jurk K, Ruggeri ZM, Massberg S, Walter U, Ruf W, Reinhardt C (2017) Gut microbiota regulate hepatic von Willebrand factor synthesis and arterial thrombus formation via Toll-like receptor-2. Blood 130(4):542–553. https://​doi.​org/​10.​1182/​blood-2016-11-754416CrossRefPubMed
82.
go back to reference Schledzewski K, Geraud C, Arnold B, Wang S, Grone HJ, Kempf T, Wollert KC, Straub BK, Schirmacher P, Demory A, Schonhaber H, Gratchev A, Dietz L, Thierse HJ, Kzhyshkowska J, Goerdt S (2011) Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors. J Clin Invest 121(2):703–714. https://doi.org/10.1172/JCI44740CrossRefPubMedPubMedCentral Schledzewski K, Geraud C, Arnold B, Wang S, Grone HJ, Kempf T, Wollert KC, Straub BK, Schirmacher P, Demory A, Schonhaber H, Gratchev A, Dietz L, Thierse HJ, Kzhyshkowska J, Goerdt S (2011) Deficiency of liver sinusoidal scavenger receptors stabilin-1 and -2 in mice causes glomerulofibrotic nephropathy via impaired hepatic clearance of noxious blood factors. J Clin Invest 121(2):703–714. https://​doi.​org/​10.​1172/​JCI44740CrossRefPubMedPubMedCentral
91.
go back to reference Carambia A, Freund B, Schwinge D, Bruns OT, Salmen SC, Ittrich H, Reimer R, Heine M, Huber S, Waurisch C, Eychmuller A, Wraith DC, Korn T, Nielsen P, Weller H, Schramm C, Luth S, Lohse AW, Heeren J, Herkel J (2015) Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. J Hepatol 62(6):1349–1356. https://doi.org/10.1016/j.jhep.2015.01.006CrossRefPubMed Carambia A, Freund B, Schwinge D, Bruns OT, Salmen SC, Ittrich H, Reimer R, Heine M, Huber S, Waurisch C, Eychmuller A, Wraith DC, Korn T, Nielsen P, Weller H, Schramm C, Luth S, Lohse AW, Heeren J, Herkel J (2015) Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice. J Hepatol 62(6):1349–1356. https://​doi.​org/​10.​1016/​j.​jhep.​2015.​01.​006CrossRefPubMed
93.
go back to reference Limmer A, Ohl J, Kurts C, Ljunggren HG, Reiss Y, Groettrup M, Momburg F, Arnold B, Knolle PA (2000) Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med 6(12):1348–1354. https://doi.org/10.1038/82161CrossRefPubMed Limmer A, Ohl J, Kurts C, Ljunggren HG, Reiss Y, Groettrup M, Momburg F, Arnold B, Knolle PA (2000) Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat Med 6(12):1348–1354. https://​doi.​org/​10.​1038/​82161CrossRefPubMed
96.
go back to reference Shetty S, Weston CJ, Oo YH, Westerlund N, Stamataki Z, Youster J, Hubscher SG, Salmi M, Jalkanen S, Lalor PF, Adams DH (2011) Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium. J Immunol 186(7):4147–4155. https://doi.org/10.4049/jimmunol.1002961CrossRefPubMed Shetty S, Weston CJ, Oo YH, Westerlund N, Stamataki Z, Youster J, Hubscher SG, Salmi M, Jalkanen S, Lalor PF, Adams DH (2011) Common lymphatic endothelial and vascular endothelial receptor-1 mediates the transmigration of regulatory T cells across human hepatic sinusoidal endothelium. J Immunol 186(7):4147–4155. https://​doi.​org/​10.​4049/​jimmunol.​1002961CrossRefPubMed
97.
98.
go back to reference Guidotti LG, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Cataudella T, Raimondi A, Gonzalez-Aseguinolaza G, Protzer U, Ruggeri ZM, Chisari FV, Isogawa M, Sitia G, Iannacone M (2015) Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell 161(3):486–500. https://doi.org/10.1016/j.cell.2015.03.005CrossRefPubMed Guidotti LG, Inverso D, Sironi L, Di Lucia P, Fioravanti J, Ganzer L, Fiocchi A, Vacca M, Aiolfi R, Sammicheli S, Mainetti M, Cataudella T, Raimondi A, Gonzalez-Aseguinolaza G, Protzer U, Ruggeri ZM, Chisari FV, Isogawa M, Sitia G, Iannacone M (2015) Immunosurveillance of the liver by intravascular effector CD8(+) T cells. Cell 161(3):486–500. https://​doi.​org/​10.​1016/​j.​cell.​2015.​03.​005CrossRefPubMed
104.
go back to reference Liu S, Yeh TH, Singh VP, Shiva S, Krauland L, Li H, Zhang P, Kharbanda K, Ritov V, Monga SP, Scott DK, Eagon PK, Behari J (2012) beta-catenin is essential for ethanol metabolism and protection against alcohol-mediated liver steatosis in mice. Hepatology 55(3):931–940. https://doi.org/10.1002/hep.24766CrossRefPubMed Liu S, Yeh TH, Singh VP, Shiva S, Krauland L, Li H, Zhang P, Kharbanda K, Ritov V, Monga SP, Scott DK, Eagon PK, Behari J (2012) beta-catenin is essential for ethanol metabolism and protection against alcohol-mediated liver steatosis in mice. Hepatology 55(3):931–940. https://​doi.​org/​10.​1002/​hep.​24766CrossRefPubMed
108.
go back to reference Zhang XJ, Olsavszky V, Yin Y, Wang B, Engleitner T, Ollinger R, Schledzewski K, Koch PS, Rad R, Schmid RM, Friess H, Goerdt S, Huser N, Geraud C, von Figura G, Hartmann D (2020) Angiocrine hepatocyte growth factor signaling controls physiological organ and body size and dynamic hepatocyte proliferation to prevent liver damage during regeneration. Am J Pathol 190(2):358–371. https://doi.org/10.1016/j.ajpath.2019.10.009CrossRefPubMed Zhang XJ, Olsavszky V, Yin Y, Wang B, Engleitner T, Ollinger R, Schledzewski K, Koch PS, Rad R, Schmid RM, Friess H, Goerdt S, Huser N, Geraud C, von Figura G, Hartmann D (2020) Angiocrine hepatocyte growth factor signaling controls physiological organ and body size and dynamic hepatocyte proliferation to prevent liver damage during regeneration. Am J Pathol 190(2):358–371. https://​doi.​org/​10.​1016/​j.​ajpath.​2019.​10.​009CrossRefPubMed
114.
go back to reference Schaffner F, Poper H (1963) Capillarization of hepatic sinusoids in man. Gastroenterology 44:239–242CrossRefPubMed Schaffner F, Poper H (1963) Capillarization of hepatic sinusoids in man. Gastroenterology 44:239–242CrossRefPubMed
117.
118.
go back to reference Desroches-Castan A, Tillet E, Ricard N, Ouarne M, Mallet C, Belmudes L, Coute Y, Boillot O, Scoazec JY, Bailly S, Feige JJ (2019) Bone morphogenetic protein 9 is a paracrine factor controlling liver sinusoidal endothelial cell fenestration and protecting against hepatic fibrosis. Hepatology 70(4):1392–1408. https://doi.org/10.1002/hep.30655CrossRefPubMed Desroches-Castan A, Tillet E, Ricard N, Ouarne M, Mallet C, Belmudes L, Coute Y, Boillot O, Scoazec JY, Bailly S, Feige JJ (2019) Bone morphogenetic protein 9 is a paracrine factor controlling liver sinusoidal endothelial cell fenestration and protecting against hepatic fibrosis. Hepatology 70(4):1392–1408. https://​doi.​org/​10.​1002/​hep.​30655CrossRefPubMed
130.
133.
go back to reference Takemura T, Yoshida Y, Kiso S, Kizu T, Furuta K, Ezaki H, Hamano M, Egawa M, Chatani N, Kamada Y, Imai Y, Higashiyama S, Iwamoto R, Mekada E, Takehara T (2013) Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice. Biochem Biophys Res Commun 437(2):185–191. https://doi.org/10.1016/j.bbrc.2013.05.097CrossRefPubMed Takemura T, Yoshida Y, Kiso S, Kizu T, Furuta K, Ezaki H, Hamano M, Egawa M, Chatani N, Kamada Y, Imai Y, Higashiyama S, Iwamoto R, Mekada E, Takehara T (2013) Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice. Biochem Biophys Res Commun 437(2):185–191. https://​doi.​org/​10.​1016/​j.​bbrc.​2013.​05.​097CrossRefPubMed
135.
go back to reference Hammoutene A, Biquard L, Lasselin J, Kheloufi M, Tanguy M, Vion AC, Merian J, Colnot N, Loyer X, Tedgui A, Codogno P, Lotersztajn S, Paradis V, Boulanger CM, Rautou PE (2020) A defect in endothelial autophagy occurs in patients with non-alcoholic steatohepatitis and promotes inflammation and fibrosis. J Hepatol 72(3):528–538. https://doi.org/10.1016/j.jhep.2019.10.028CrossRefPubMed Hammoutene A, Biquard L, Lasselin J, Kheloufi M, Tanguy M, Vion AC, Merian J, Colnot N, Loyer X, Tedgui A, Codogno P, Lotersztajn S, Paradis V, Boulanger CM, Rautou PE (2020) A defect in endothelial autophagy occurs in patients with non-alcoholic steatohepatitis and promotes inflammation and fibrosis. J Hepatol 72(3):528–538. https://​doi.​org/​10.​1016/​j.​jhep.​2019.​10.​028CrossRefPubMed
139.
go back to reference Xiong X, Kuang H, Ansari S, Liu T, Gong J, Wang S, Zhao XY, Ji Y, Li C, Guo L, Zhou L, Chen Z, Leon-Mimila P, Chung MT, Kurabayashi K, Opp J, Campos-Perez F, Villamil-Ramirez H, Canizales-Quinteros S, Lyons R, Lumeng CN, Zhou B, Qi L, Huertas-Vazquez A, Lusis AJ, Xu XZS, Li S, Yu Y, Li JZ, Lin JD (2019) Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol Cell 75(3):644-660 e645. https://doi.org/10.1016/j.molcel.2019.07.028CrossRefPubMedPubMedCentral Xiong X, Kuang H, Ansari S, Liu T, Gong J, Wang S, Zhao XY, Ji Y, Li C, Guo L, Zhou L, Chen Z, Leon-Mimila P, Chung MT, Kurabayashi K, Opp J, Campos-Perez F, Villamil-Ramirez H, Canizales-Quinteros S, Lyons R, Lumeng CN, Zhou B, Qi L, Huertas-Vazquez A, Lusis AJ, Xu XZS, Li S, Yu Y, Li JZ, Lin JD (2019) Landscape of intercellular crosstalk in healthy and NASH liver revealed by single-cell secretome gene analysis. Mol Cell 75(3):644-660 e645. https://​doi.​org/​10.​1016/​j.​molcel.​2019.​07.​028CrossRefPubMedPubMedCentral
140.
go back to reference Ramachandran P, Dobie R, Wilson-Kanamori JR, Dora EF, Henderson BEP, Luu NT, Portman JR, Matchett KP, Brice M, Marwick JA, Taylor RS, Efremova M, Vento-Tormo R, Carragher NO, Kendall TJ, Fallowfield JA, Harrison EM, Mole DJ, Wigmore SJ, Newsome PN, Weston CJ, Iredale JP, Tacke F, Pollard JW, Ponting CP, Marioni JC, Teichmann SA, Henderson NC (2019) Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575(7783):512–518. https://doi.org/10.1038/s41586-019-1631-3CrossRefPubMedPubMedCentral Ramachandran P, Dobie R, Wilson-Kanamori JR, Dora EF, Henderson BEP, Luu NT, Portman JR, Matchett KP, Brice M, Marwick JA, Taylor RS, Efremova M, Vento-Tormo R, Carragher NO, Kendall TJ, Fallowfield JA, Harrison EM, Mole DJ, Wigmore SJ, Newsome PN, Weston CJ, Iredale JP, Tacke F, Pollard JW, Ponting CP, Marioni JC, Teichmann SA, Henderson NC (2019) Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature 575(7783):512–518. https://​doi.​org/​10.​1038/​s41586-019-1631-3CrossRefPubMedPubMedCentral
141.
go back to reference Terkelsen MK, Bendixen SM, Hansen D, Scott EAH, Moeller AF, Nielsen R, Mandrup S, Schlosser A, Andersen TL, Sorensen GL, Krag A, Natarajan KN, Detlefsen S, Dimke H, Ravnskjaer K (2020) Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury. Hepatology 72(6):2119–2133. https://doi.org/10.1002/hep.31215CrossRefPubMed Terkelsen MK, Bendixen SM, Hansen D, Scott EAH, Moeller AF, Nielsen R, Mandrup S, Schlosser A, Andersen TL, Sorensen GL, Krag A, Natarajan KN, Detlefsen S, Dimke H, Ravnskjaer K (2020) Transcriptional dynamics of hepatic sinusoid-associated cells after liver injury. Hepatology 72(6):2119–2133. https://​doi.​org/​10.​1002/​hep.​31215CrossRefPubMed
143.
go back to reference Geraud C, Mogler C, Runge A, Evdokimov K, Lu S, Schledzewski K, Arnold B, Hammerling G, Koch PS, Breuhahn K, Longerich T, Marx A, Weiss C, Damm F, Schmieder A, Schirmacher P, Augustin HG, Goerdt S (2013) Endothelial transdifferentiation in hepatocellular carcinoma: Loss of Stabilin-2 expression in peri-tumourous liver correlates with increased survival. Liver Int 33(9):1428–1440. https://doi.org/10.1111/liv.12262CrossRefPubMed Geraud C, Mogler C, Runge A, Evdokimov K, Lu S, Schledzewski K, Arnold B, Hammerling G, Koch PS, Breuhahn K, Longerich T, Marx A, Weiss C, Damm F, Schmieder A, Schirmacher P, Augustin HG, Goerdt S (2013) Endothelial transdifferentiation in hepatocellular carcinoma: Loss of Stabilin-2 expression in peri-tumourous liver correlates with increased survival. Liver Int 33(9):1428–1440. https://​doi.​org/​10.​1111/​liv.​12262CrossRefPubMed
146.
go back to reference Sharma A, Seow JJW, Dutertre CA, Pai R, Bleriot C, Mishra A, Wong RMM, Singh GSN, Sudhagar S, Khalilnezhad S, Erdal S, Teo HM, Khalilnezhad A, Chakarov S, Lim TKH, Fui ACY, Chieh AKW, Chung CP, Bonney GK, Goh BK, Chan JKY, Chow PKH, Ginhoux F, DasGupta R (2020) Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell 183(2):377–394. https://doi.org/10.1016/j.cell.2020.08.040CrossRefPubMed Sharma A, Seow JJW, Dutertre CA, Pai R, Bleriot C, Mishra A, Wong RMM, Singh GSN, Sudhagar S, Khalilnezhad S, Erdal S, Teo HM, Khalilnezhad A, Chakarov S, Lim TKH, Fui ACY, Chieh AKW, Chung CP, Bonney GK, Goh BK, Chan JKY, Chow PKH, Ginhoux F, DasGupta R (2020) Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in hepatocellular carcinoma. Cell 183(2):377–394. https://​doi.​org/​10.​1016/​j.​cell.​2020.​08.​040CrossRefPubMed
151.
go back to reference Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, Ledergor G, Jung Y, Milo I, Poulos MG, Kalinkovich A, Ludin A, Kollet O, Shakhar G, Butler JM, Rafii S, Adams RH, Scadden DT, Lin CP, Lapidot T (2016) Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 532(7599):323–328. https://doi.org/10.1038/nature17624CrossRefPubMedPubMedCentral Itkin T, Gur-Cohen S, Spencer JA, Schajnovitz A, Ramasamy SK, Kusumbe AP, Ledergor G, Jung Y, Milo I, Poulos MG, Kalinkovich A, Ludin A, Kollet O, Shakhar G, Butler JM, Rafii S, Adams RH, Scadden DT, Lin CP, Lapidot T (2016) Distinct bone marrow blood vessels differentially regulate haematopoiesis. Nature 532(7599):323–328. https://​doi.​org/​10.​1038/​nature17624CrossRefPubMedPubMedCentral
157.
159.
go back to reference Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL, Investigators IM (2020) Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905. https://doi.org/10.1056/NEJMoa1915745CrossRefPubMed Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, Kudo M, Breder V, Merle P, Kaseb AO, Li D, Verret W, Xu DZ, Hernandez S, Liu J, Huang C, Mulla S, Wang Y, Lim HY, Zhu AX, Cheng AL, Investigators IM (2020) Atezolizumab plus Bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med 382(20):1894–1905. https://​doi.​org/​10.​1056/​NEJMoa1915745CrossRefPubMed
Metadata
Title
Angiodiversity and organotypic functions of sinusoidal endothelial cells
Authors
Philipp-Sebastian Koch
Ki Hong Lee
Sergij Goerdt
Hellmut G. Augustin
Publication date
01-05-2021
Publisher
Springer Netherlands
Published in
Angiogenesis / Issue 2/2021
Print ISSN: 0969-6970
Electronic ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-021-09780-y

Other articles of this Issue 2/2021

Angiogenesis 2/2021 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.