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Current Hepatology Reports
Erschienen in: Current Hepatology Reports 2/2019

16.05.2019 | Portal Hypertension (J Gonzalez-Abraldes and E Tsochatzis, Section Editors)

The Role of Hepatic and Splanchnic Lymphatic System in Portal Hypertension and Ascites

verfasst von: Jordi Ribera, Bernat Córdoba-Jover, Irene Portolés, Manuel Morales-Ruiz

Erschienen in: Current Hepatology Reports | Ausgabe 2/2019

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Abstract

Purpose of Review

The lymphatic network plays a major role in maintaining tissue fluid homeostasis. Therefore, several pathological conditions associated with edema formation result in deficient lymphatic function. However, traditionally, the lymphatic system has been underestimated until recent years when it has been noticed the importance of this system in chronic liver disease. This review highlights the knowledge of lymphatic biology in the context of portal hypertension and liver cirrhosis.

Recent Findings

Among different roles of lymphatic system in liver disease, two remarkable ones are the contribution in ascites accumulation and the hepatic lymphangiogenesis in portal hypertension which is regulated by sympathetic nerves.

Summary

The identification of novel pathological mechanisms has focused efforts into correction of structural changes and function affecting lymphatic vessels in liver disease. Despite the knowledge gained, we still have to face many unresolved questions concerning the role played by the lymphatic system in chronic liver disease and the design of therapeutic targeting.
Literatur
1.
Jurisic G, Detmar M. Lymphatic endothelium in health and disease. Cell Tissue Res. 2009;335:97–108.CrossRefPubMed
2.
Olszewski WL. The innate reaction of the human skin lymphatic system to foreign and self-antigens. Lymphat Res Biol. 2005;3:50–7.CrossRefPubMed
3.
Bruyè F, Noël AS. Lymphangiogenesis: in vitro and in vivo models. FASEB J. 2010;24:8–21.CrossRef
4.
Halin C, Detmar M. An unexpected connection: lymph node lymphangiogenesis and dendritic cell migration. Immunity. 2006;24:129–31.CrossRefPubMed
5.
Szuba A, Rockson SG. Lymphedema: anatomy, physiology and pathogenesis. Vasc Med. 1997;2:321–6.CrossRefPubMed
6.
Shin WS, Rockson SG. Animal models for the molecular and mechanistic study of lymphatic biology and disease. Ann N Y Acad Sci. 2008;1131:50–74.CrossRefPubMed
7.
8.
9.
Hägerling R, Pollmann C, Andreas M, Schmidt C, Nurmi H, Adams RH, et al. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J. 2013;32:629–44.CrossRefPubMedPubMedCentral
10.
Yang Y, García-Verdugo JM, Soriano-Navarro M, Srinivasan RS, Scallan JP, Singh MK, et al. Lymphatic endothelial progenitors bud from the cardinal vein and intersomitic vessels in mammalian embryos. Blood. 2012;120:2340–8.CrossRefPubMedPubMedCentral
11.
Yaniv K, Isogai S, Castranova D, Dye L, Hitomi J, Weinstein BM. Live imaging of lymphatic development in the zebrafish. Nat Med. 2006;12:711–6.CrossRefPubMed
12.
Buttler K, Kreysing A, von Kaisenberg CS, Schweigerer L, Gale N, Papoutsi M, et al. Mesenchymal cells with leukocyte and lymphendothelial characteristics in murine embryos. Dev Dyn. 2006;235:1554–62.CrossRefPubMed
13.
Mahadevan A, Welsh IC, Sivakumar A, Gludish DW, Shilvock AR, Noden DM, et al. The left-right Pitx2 pathway drives organ-specific arterial and lymphatic development in the intestine. Dev Cell. 2014;31:690–706.CrossRefPubMedPubMedCentral
14.
• Stanczuk L, Martinez-Corral I, Ulvmar MH, Zhang Y, Laviña B, Fruttiger M, et al. cKit lineage hemogenic endothelium-derived cells contribute to mesenteric lymphatic vessels. Cell Rep. 2015;10:1708–21 This study demonstrates that part of the mesenteric lymphatic vasculature develops from cKit lineage cells of hemogenic endothelial origin, breaking the current dogma that all mammalian lymphatic vessels form by sprouting from veins. CrossRefPubMed
15.
Klotz L, Norman S, Vieira JM, Masters M, Rohling M, Dubé KN, et al. Cardiac lymphatics are heterogeneous in origin and respond to injury. Nature. 2015;522:62–7.CrossRefPubMedPubMedCentral
16.
Martinez-Corral I, Ulvmar MH, Stanczuk L, Tatin F, Kizhatil K, John SWM, et al. Nonvenous origin of dermal lymphatic vasculature. Circ Res. 2015;116:1649–54.CrossRefPubMed
17.
Wigle JT, Oliver G. Prox1 function is required for the development of the murine lymphatic system. Cell. 1999;98:769–78.CrossRefPubMed
18.
Wigle JT, Harvey N, Detmar M, Lagutina I, Grosveld G, Gunn MD, et al. An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. EMBO J. 2002;21:1505–13.CrossRefPubMedPubMedCentral
19.
Escobedo N, Oliver G. Lymphangiogenesis: origin, specification, and cell fate determination. Annu Rev Cell Dev Biol. 2016;32:677–91.CrossRefPubMed
20.
Yamazaki T, Yoshimatsu Y, Morishita Y, Miyazono K, Watabe T. COUP-TFII regulates the functions of Prox1 in lymphatic endothelial cells through direct interaction. Genes Cells. 2009;14:425–34.CrossRefPubMed
21.
• Ma W, Oliver G. Lymphatic endothelial cell plasticity in development and disease. Physiology. 2017;32:444–52 A review where the authors provide an overview of the molecular mechanisms promoting lymphatic cell fate specification in the mammalian embryo and summarize available data suggesting that lymphatic EC fate is reprogrammable in normal and pathological settings. CrossRefPubMedPubMedCentral
22.
Sabin FR. On the origin of the lymphatic system from the veins and the development of the lymph hearts and thoracic duct in the pig. Am J Anat. 1902;1:367–89.CrossRef
23.
Schacht V, Ramirez MI, Hong Y-K, Hirakawa S, Feng D, Harvey N, et al. T1alpha/podoplanin deficiency disrupts normal lymphatic vasculature formation and causes lymphedema. EMBO J. 2003;22:3546–56.CrossRefPubMedPubMedCentral
24.
Karpanen T, Wirzenius M, Mäkinen T, Veikkola T, Haisma HJ, Achen MG, et al. Lymphangiogenic growth factor responsiveness is modulated by postnatal lymphatic vessel maturation. Am J Pathol. 2006;169:708–18.CrossRefPubMedPubMedCentral
25.
Srinivasan RS, Escobedo N, Yang Y, Interiano A, Dillard ME, Finkelstein D, et al. The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors. Genes Dev. 2014;28:2175–87.CrossRefPubMedPubMedCentral
26.
Fritz-Six KL, Dunworth WP, Li M, Caron KM. Adrenomedullin signaling is necessary for murine lymphatic vascular development. J Clin Invest. 2008;118:40–50.CrossRefPubMed
27.
Murtomaki A, Uh MK, Choi YK, Kitajewski C, Borisenko V, Kitajewski J, et al. Notch1 functions as a negative regulator of lymphatic endothelial cell differentiation in the venous endothelium. Development. 2013;140:2365–76.CrossRefPubMedPubMedCentral
28.
Pedrioli DML, Karpanen T, Dabouras V, Jurisic G, van de Hoek G, Shin JW, et al. miR-31 functions as a negative regulator of lymphatic vascular lineage-specific differentiation in vitro and vascular development in vivo. Mol Cell Biol. 2010;30:3620–34.CrossRefPubMed
29.
Kazenwadel J, Michael MZ, Harvey NL. Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood. 2010;116:2395–401.CrossRefPubMed
30.
Seo M, Choi J-S, Rho C, Joo C-K, Lee S. MicroRNA miR-466 inhibits lymphangiogenesis by targeting prospero-related homeobox 1 in the alkali burn corneal injury model. J Biomed Sci. 2015;22:3.CrossRefPubMedPubMedCentral
31.
Abtahian F, Guerriero A, Sebzda E, Lu M-M, Zhou R, Mocsai A, et al. Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science. 2003;299:247–51.CrossRefPubMedPubMedCentral
32.
Sebzda E, Hibbard C, Sweeney S, Abtahian F, Bezman N, Clemens G, et al. Syk and Slp-76 mutant mice reveal a cell-autonomous hematopoietic cell contribution to vascular development. Dev Cell. 2006;11:349–61.CrossRefPubMed
33.
Christou CM, Pearce AC, Watson AA, Mistry AR, Pollitt AY, Fenton-May AE, et al. Renal cells activate the platelet receptor CLEC-2 through podoplanin. Biochem J. 2008;411:133–40.CrossRefPubMedPubMedCentral
34.
Suzuki-Inoue K, Kato Y, Inoue O, Kaneko MK, Mishima K, Yatomi Y, et al. Involvement of the snake toxin receptor CLEC-2, in podoplanin-mediated platelet activation, by cancer cells. J Biol Chem. 2007;282:25993–6001.CrossRef
35.
Bäckhed F, Crawford PA, O’Donnell D, Gordon JI. Postnatal lymphatic partitioning from the blood vasculature in the small intestine requires fasting-induced adipose factor. Proc Natl Acad Sci U S A. 2007;104:606–11.CrossRefPubMedPubMedCentral
36.
37.
Julenius K, Mølgaard A, Gupta R, Brunak S. Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites. Glycobiology. 2005;15:153–64.CrossRefPubMed
38.
•• Tanaka M, Iwakiri Y. The hepatic lymphatic vascular system: structure, function, markers, and lymphangiogenesis. Cell Mol Gastroenterol Hepatol. 2016;2:733–49 This article reviews the current knowledge of the structure, function, and markers of the hepatic lymphatic vascular system as well as factors associated with hepatic lymphangiogenesis and compares liver lymphatics with those in other tissues. CrossRefPubMedPubMedCentral
39.
Ohtani O, Ohtani Y. Lymph circulation in the liver. Anat Rec Adv Integr Anat Evol Biol. 2008;291:643–52.CrossRef
40.
• Tanaka M, Iwakiri Y. Lymphatics in the liver. Curr Opin Immunol. 2018;53:137–42 A review article addressing the potential role of lymphatic endothelial cells in the health and the disease of the liver. CrossRefPubMed
41.
Dumont AE, Mulholland JH. Alterations in thoracic duct lymph flow in hepatic cirrhosis: significance in portal hypertension. Ann Surg. 1962;156:668–75.CrossRefPubMedPubMedCentral
42.
Witte CL, Witte MH, Dumont AE, Frist J, Cole WR. Lymph protein in hepatic cirrhosis and experimental hepatic and portal venous hypertension. Ann Surg. 1968;168:567–77.CrossRefPubMedPubMedCentral
43.
Corpechot C, Barbu V, Wendum D, Kinnman N, Rey C, Poupon R, et al. Hypoxia-induced VEGF and collagen I expressions are associated with angiogenesis and fibrogenesis in experimental cirrhosis. Hepatology. 2002;35:1010–21.CrossRefPubMed
44.
Tugues S, Morales-Ruiz M, Fernandez-Varo G, Ros J, Arteta D, Muñoz-Luque J, et al. Microarray analysis of endothelial differentially expressed genes in liver of cirrhotic rats. Gastroenterology. 2005;129:1686–95.CrossRefPubMed
45.
46.
47.
• Tanaka M, Utsumi T, Saruwatari J, Zhang PP, Morales-Ruiz M, Iwakiri Y, et al. The sympathetic nervous system is a novel regulator of hepatic lymphangiogenesis in portal hypertension. Hepatology. 2018;68:772A Abstract indicating a link between sympathetic nervous system activation and liver lymphangiogenesis, sympathetic nerves are a key regulator of hepatic lymphangiogenesis by secreting VEGF-C in rats with portal hypertension.
48.
Dumont AE, Mulholland JH. Flow rate and composition of thoracic-duct lymph in patients with cirrhosis. N Engl J Med. 1960;263:471–4.CrossRefPubMed
49.
Sadek AM, Ismail AM, Aboul Enein A, Hassanein E, Massoud OG, El-Assi MH. Percutaneous trans hepatic lymphography: evaluation in schistosomal hepatic fibrosis. Lymphology. 1976;9:47–52.PubMed
50.
Shimada Y. Observations on hepatic superficial lymph flow. Lymphology. 1979;12:11–3.PubMed
51.
Niiyama G. A scanning electron microscopic study of subcapsular lymphatic capillaries of the normal liver and the liver in Budd-Chiari syndrome after chemical digestion. Kawasaki Med J. 1994;20:37–52.
52.
Vollmar B, Wolf B, Siegmund S, Katsen AD, Menger MD. Lymph vessel expansion and function in the development of hepatic fibrosis and cirrhosis. Am J Pathol. 1997;151:169–75.PubMedPubMedCentral
53.
Yamauchi Y, Michitaka K, Onji M. Morphometric analysis of lymphatic and blood vessels in human chronic viral liver diseases. Am J Pathol. 1998;153:1131–7.CrossRefPubMedPubMedCentral
54.
Yokomori H, Oda M, Kaneko F, Kawachi S, Tanabe M, Yoshimura K, et al. Lymphatic marker podoplanin/D2-40 in human advanced cirrhotic liver--re-evaluations of microlymphatic abnormalities. BMC Gastroenterol. 2010;10:131.CrossRefPubMedPubMedCentral
55.
Henriksen JH. Estimation of lymphatic conductance. A model based on protein-kinetic studies and haemodynamic measurements in patients with cirrhosis of the liver and in pigs. Scand J Clin Lab Invest. 1985;45:123–30.CrossRefPubMed
56.
Ribera J, Pauta M, Melgar-Lesmes P, Tugues S, Fernández-Varo G, Held KF, et al. Increased nitric oxide production in lymphatic endothelial cells causes impairment of lymphatic drainage in cirrhotic rats. Gut. 2013;62:138–45.CrossRefPubMed
57.
Aukland K, Reed RK. Interstitial-lymphatic mechanisms in the control of extracellular fluid volume. Physiol Rev. 1993;73:1–78.CrossRefPubMed
58.
Hagendoorn J, Padera TP, Kashiwagi S, Isaka N, Noda F, Lin MI, et al. Endothelial nitric oxide synthase regulates microlymphatic flow via collecting lymphatics. Circ Res. 2004;95:204–9.CrossRefPubMed
59.
Witte CL, Witte MH, Dumont AE. Lymph imbalance in the genesis and perpetuation of the ascites syndrome in hepatic cirrhosis. Gastroenterology. 1980;78:1059–68.CrossRefPubMed
60.
Arroyo V. Pathophysiology, diagnosis and treatment of ascites in cirrhosis. Ann Hepatol. 2002;1:72–9.CrossRef
61.
Rector WG. Spontaneous chylous ascites of cirrhosis. J Clin Gastroenterol. 1984;6:369–72.PubMed
62.
Cheng WSC, Gough IR, Ward M, Croese J, Powell LW. Chylous ascites in cirrhosis: a case report and review of the literature. J Gastroenterol Hepatol. 1989;4:95–9.CrossRefPubMed
63.
Almakdisi T, Massoud S, Makdisi G. Lymphomas and chylous ascites: review of the literature. Oncologist. 2005;10:632–5.CrossRefPubMed
Metadaten
Titel
The Role of Hepatic and Splanchnic Lymphatic System in Portal Hypertension and Ascites
verfasst von
Jordi Ribera
Bernat Córdoba-Jover
Irene Portolés
Manuel Morales-Ruiz
Publikationsdatum
16.05.2019
Verlag
Springer US
Erschienen in
Current Hepatology Reports / Ausgabe 2/2019
Elektronische ISSN: 2195-9595
DOI
https://doi.org/10.1007/s11901-019-00460-6

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