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European Surgery
Erschienen in:

01.12.2015 | Review

The role of platelets and portal venous pressure fluctuations in postoperative liver regeneration

verfasst von: P. Starlinger, MD, PhD, A. Assinger, T. Gruenberger, C. Brostjan

Erschienen in: European Surgery | Ausgabe 6/2015

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Summary

Background

The most relevant factor predicting morbidity and mortality after liver resection is the ability of the remnant liver to regenerate. In line with extensive experimental research, we were recently able to demonstrate that serotonin and thrombospondin-1, two factors abundantly stored in platelets, are closely associated with liver regeneration of patients after liver resection.

Methods

Within this review, we summarized existing evidence regarding the relevance of platelets in liver regeneration.

Results

We illustrated a potential interaction of platelet activation and its relation to portal venous pressure during the process of liver regeneration.

Conclusions

We are able to explore possible effects of specific granule release as a key regulator to allow for platelet-induced liver regeneration. As a second objective, we discussed postoperative portal venous pressure as a potential mechanism and initiating effect in postoperative platelet activation during liver regeneration which may offer new therapeutic targets to promote postoperative liver regeneration.
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Literatur
1.
Simmonds PC, Primrose JN, Colquitt JL, Garden OJ, Poston GJ, Rees M. Surgical resection of hepatic metastases from colorectal cancer: a systematic review of published studies. Br J Cancer. 2006;94(7):982–99.PubMedCentralCrossRefPubMed
2.
Van Cutsem E, Nordlinger B, Adam R, Kohne CH, Pozzo C, Poston G, et al. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer. 2006;42(14):2212–21.CrossRefPubMed
3.
Kopetz S, Chang GJ, Overman MJ, Eng C, Sargent DJ, Larson DW, et al. Improved survival in metastatic colorectal cancer is associated with adoption of hepatic resection and improved chemotherapy. J Clin Oncol. 2009;27(22):3677–83.PubMedCentralCrossRefPubMed
4.
Abdalla EK, Adam R, Bilchik AJ, Jaeck D, Vauthey JN, Mahvi D. Improving resectability of hepatic colorectal metastases: expert consensus statement. Ann Surg Oncol. 2006;13(10):1271–80.CrossRefPubMed
5.
Wei AC, Tung-Ping Poon R, Fan ST, Wong J. Risk factors for perioperative morbidity and mortality after extended hepatectomy for hepatocellular carcinoma. Br J Surg. 2003;90(1):33–41.CrossRefPubMed
6.
Mullen JT, Ribero D, Reddy SK, Donadon M, Zorzi D, Gautam S, et al. Hepatic insufficiency and mortality in 1,059 noncirrhotic patients undergoing major hepatectomy. J Am Coll Surg. 2007;204(5):854–62.CrossRefPubMed
7.
Starlinger P, Assinger A, Haegele S, Wanek D, Zikeli S, Schauer D, et al. Evidence for serotonin as a relevant inducer of liver regeneration after liver resection in humans. Hepatology. 2014;60(1):257–66.CrossRefPubMed
8.
Starlinger P, Brostjan C, Gruenberger T. Evidence for serotonin as an inducer of liver regeneration in humans—further investigations. Hepatology. 2015;62(3):984. doi:10.1002/hep.27672.
9.
Starlinger P, Haegele S, Wanek D, Zikeli S, Schauer D, Alidzanovic L, et al. Plasma thrombospondin 1 as a predictor of postoperative liver dysfunction. Br J Surg. 2015;102(7):826–36.CrossRefPubMed
10.
Starlinger P, Schauer D, Alidzanovic L, Zikeli S, Gebhardt K, Luf F, et al. Clinical evidence for thrombospondin-1 as a relevant suppressor of liver regeneration. J Hepatol. 2013;58(5):1053–4.CrossRefPubMed
11.
Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology. 2006;43(2 Suppl 1):S45–53.CrossRefPubMed
12.
13.
Sakamoto T, Liu Z, Murase N, Ezure T, Yokomuro S, Poli V, et al. Mitosis and apoptosis in the liver of interleukin-6-deficient mice after partial hepatectomy. Hepatology. 1999;29(2):403–11.CrossRefPubMed
14.
Yin C, Evason KJ, Asahina K, Stainier DY. Hepatic stellate cells in liver development, regeneration, and cancer. J Clin Invest. 2013;123(5):1902–10.PubMedCentralCrossRefPubMed
15.
Wagenaar GT, Chamuleau RA, Pool CW, de Haan JG, Maas MA, Korfage HA, et al. Distribution and activity of glutamine synthase and carbamoylphosphate synthase upon enlargement of the liver lobule by repeated partial hepatectomies. J Hepatol. 1993;17(3):397–407.CrossRefPubMed
16.
17.
Clavien PA. Liver regeneration: a spotlight on the novel role of platelets and serotonin. Swiss Med Wkly. 2008;138(25–26):361–70.PubMed
18.
Murata S, Matsuo R, Ikeda O, Myronovych A, Watanabe M, Hisakura K, et al. Platelets promote liver regeneration under conditions of Kupffer cell depletion after hepatectomy in mice. World J Surg. 2008;32(6):1088–96.CrossRefPubMed
19.
Tomikawa M, Hashizume M, Highashi H, Ohta M, Sugimachi K. The role of the spleen, platelets, and plasma hepatocyte growth factor activity on hepatic regeneration in rats. J Am Coll Surg. 1996;182(1):12–6.PubMed
20.
Murata S, Ohkohchi N, Matsuo R, Ikeda O, Myronovych A, Hoshi R. Platelets promote liver regeneration in early period after hepatectomy in mice. World J Surg. 2007;31(4):808–16.CrossRefPubMed
21.
Lesurtel M, Graf R, Aleil B, Walther DJ, Tian Y, Jochum W, et al. Platelet-derived serotonin mediates liver regeneration. Science. 2006;312(5770):104–7.CrossRefPubMed
22.
Myronovych A, Murata S, Chiba M, Matsuo R, Ikeda O, Watanabe M, et al. Role of platelets on liver regeneration after 90 % hepatectomy in mice. J Hepatol. 2008;49(3):363–72.CrossRefPubMed
23.
Matsuo R, Nakano Y, Ohkohchi N. Platelet administration via the portal vein promotes liver regeneration in rats after 70 % hepatectomy. Ann Surg. 2011;253(4):759–63.CrossRefPubMed
24.
Kaneko K, Shirai Y, Wakai T, Yokoyama N, Akazawa K, Hatakeyama K. Low preoperative platelet counts predict a high mortality after partial hepatectomy in patients with hepatocellular carcinoma. World J Gastroenterol. 2005;11(37):5888–92.PubMedCentralCrossRefPubMed
25.
Soubrane O, Brouquet A, Zalinski S, Terris B, Brezault C, Mallet V, et al. Predicting high grade lesions of sinusoidal obstruction syndrome related to oxaliplatin-based chemotherapy for colorectal liver metastases: correlation with post-hepatectomy outcome. Ann Surg. 2010;251(3):454–60.CrossRefPubMed
26.
Alkozai EM, Nijsten MW, de Jong KP, de Boer MT, Peeters PM, Slooff MJ, et al. Immediate postoperative low platelet count is associated with delayed liver function recovery after partial liver resection. Ann Surg. 2010;251(2):300–6.CrossRefPubMed
27.
Haegele S, Offensperger F, Pereyra D, Lahner E, Assinger A, Fleischmann E, et al. Deficiency in thrombopoietin induction after liver surgery is associated with postoperative liver dysfunction. PloS One. 2015;10(1):e0116985.PubMedCentralCrossRefPubMed
28.
29.
Starlinger P, Alidzanovic L, Schauer D, Brugger P, Sommerfeldt S, Kuehrer I, et al. Platelet-stored angiogenesis factors: clinical monitoring is prone to artifacts. Dis Markers. 2011;31(2):55–65.PubMedCentralCrossRefPubMed
30.
Balasubramanian S, Paulose CS. Induction of DNA synthesis in primary cultures of rat hepatocytes by serotonin: possible involvement of serotonin S2 receptor. Hepatology. 1998;27(1):62–6.CrossRefPubMed
31.
Sulaiman P, Joseph B, Kaimal SB, Paulose CS. Decreased hepatic 5-HT1A receptors during liver regeneration and neoplasia in rats. Neurochem Res. 2008;33(3):444–9.CrossRefPubMed
32.
Nagao Y, Akahoshi T, Kamori M, Uehara H, Hashimoto N, Kinjo N, et al. Liver regeneration is promoted by increasing serotonin content in rat liver with secondary biliary cirrhosis. Hepatol Res. 2011;41(8):784–94.CrossRefPubMed
33.
Papadimas GK, Tzirogiannis KN, Panoutsopoulos GI, Demonakou MD, Skaltsas SD, Hereti RI, et al. Effect of serotonin receptor 2 blockage on liver regeneration after partial hepatectomy in the rat liver. Liver Int. 2006;26(3):352–61.CrossRefPubMed
34.
Liu Y, Zhang ZY. Serotonin receptor agonist quipazine promotes proliferation and apoptosis of human hepatocyte strain of L-02 strain. Hepatobiliary Pancreat Dis Int. 2009;8(3):278–81.PubMed
35.
Tian Y, Graf R, El-Badry AM, Lesurtel M, Furrer K, Moritz W, et al. Activation of serotonin receptor-2B rescues small-for-size liver graft failure in mice. Hepatology. 2011;53(1):253–62.CrossRefPubMed
36.
Italiano JE Jr, Richardson JL, Patel-Hett S, Battinelli E, Zaslavsky A, Short S, et al. Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. Blood. 2008;111(3):1227–33.PubMedCentralCrossRefPubMed
37.
Kamykowski J, Carlton P, Sehgal S, Storrie B. Quantitative immunofluorescence mapping reveals little functional coclustering of proteins within platelet alpha-granules. Blood. 2011;118(5):1370–3.CrossRefPubMed
38.
Jonnalagadda D, Izu LT, Whiteheart SW. Platelet secretion is kinetically heterogeneous in an agonist-responsive manner. Blood. 2012;120(26):5209–16.PubMedCentralCrossRefPubMed
39.
Battinelli EM, Markens BA, Italiano JE Jr. Release of angiogenesis regulatory proteins from platelet alpha granules: modulation of physiologic and pathologic angiogenesis. Blood. 2011;118(5):1359–69.PubMedCentralCrossRefPubMed
40.
Chatterjee M, Huang Z, Zhang W, Jiang L, Hultenby K, Zhu L, et al. Distinct platelet packaging, release, and surface expression of proangiogenic and antiangiogenic factors on different platelet stimuli. Blood. 2011;117(14):3907–11.CrossRefPubMed
41.
Furrer K, Rickenbacher A, Tian Y, Jochum W, Bittermann AG, Kach A, et al. Serotonin reverts age-related capillarization and failure of regeneration in the liver through a VEGF-dependent pathway. Proc Natl Acad Sci USA. 2011;108(7):2945–50.PubMedCentralCrossRefPubMed
42.
Bockhorn M, Goralski M, Prokofiev D, Dammann P, Grunewald P, Trippler M, et al. VEGF is important for early liver regeneration after partial hepatectomy. J Surg Res. 2007;138(2):291–9.CrossRefPubMed
43.
Oe H, Kaido T, Mori A, Onodera H, Imamura M. Hepatocyte growth factor as well as vascular endothelial growth factor gene induction effectively promotes liver regeneration after hepatectomy in Solt-Farber rats. Hepatogastroenterology. 2005;52(65):1393–7.PubMed
44.
Taniguchi E, Sakisaka S, Matsuo K, Tanikawa K, Sata M. Expression and role of vascular endothelial growth factor in liver regeneration after partial hepatectomy in rats. J Histochem Cytochem. 2001;49(1):121–30.CrossRefPubMed
45.
Hayashi H, Sakai K, Baba H, Sakai T. Thrombospondin-1 is a novel negative regulator of liver regeneration after partial hepatectomy through transforming growth factor-beta1 activation in mice. Hepatology. 2012;55(5):1562–73.PubMedCentralCrossRefPubMed
46.
Bonnefoy A, Moura R, Hoylaerts MF. The evolving role of thrombospondin-1 in hemostasis and vascular biology. Cell Mol Life Sci. 2008;65(5):713–27.CrossRefPubMed
47.
Starlinger P, Moll HP, Assinger A, Nemeth C, Hoetzenecker K, Gruenberger B, et al. Thrombospondin-1: a unique marker to identify in vitro platelet activation when monitoring in vivo processes. J Thromb Haemost. 2010;8(8):1809–19.CrossRefPubMed
48.
49.
Adams JC, Bentley AA, Kvansakul M, Hatherley D, Hohenester E. Extracellular matrix retention of thrombospondin 1 is controlled by its conserved C-terminal region. J Cell Sci. 2008;121(Pt 6):784–95.CrossRefPubMed
50.
Kuroki H, Hayashi H, Nakagawa S, Sakamoto K, Higashi T, Nitta H, et al. Effect of LSKL peptide on thrombospondin 1-mediated transforming growth factor beta signal activation and liver regeneration after hepatectomy in an experimental model. Br J Surg. 2015;102(7):813–25.PubMedCentralCrossRefPubMed
51.
Li J, Liang L, Ma T, Yu X, Chen W, Xu G, et al. Sinusoidal microcirculatory changes after small-for-size liver transplantation in rats. Transpl Int. 2010;23(9):924–33.PubMed
52.
Asencio JM, Vaquero J, Olmedilla L, Garcia Sabrido JL. “Small-for-flow” syndrome: shifting the “size” paradigm. Med Hypotheses. 2013;80(5):573–7.CrossRefPubMed
53.
May D, Djonov V, Zamir G, Bala M, Safadi R, Sklair-Levy M, et al. 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(7):e21478.PubMedCentralCrossRefPubMed
54.
Morsiani E, Aleotti A, Ricci D. Haemodynamic and ultrastructural observations on the rat liver after two-thirds partial hepatectomy. J Anat. 1998;192(Pt 4):507–15.PubMedCentralCrossRefPubMed
55.
Fahrner R, Patsenker E, de Gottardi A, Stickel F, Montani M, Stroka D, et al. Elevated liver regeneration in response to pharmacological reduction of elevated portal venous pressure by terlipressin after partial hepatectomy. Transplantation. 2014;97(9):892–900.CrossRefPubMed
56.
Abshagen K, Eipel C, Vollmar B. A critical appraisal of the hemodynamic signal driving liver regeneration. Langenbecks Arch Surg. 2012;397(4):579–90.CrossRefPubMed
57.
Mortensen KE, Conley LN, Nygaard I, Sorenesen P, Mortensen E, Bendixen C, et al. Increased sinusoidal flow is not the primary stimulus to liver regeneration. Comp Hepatol. 2010;9:2.PubMedCentralCrossRefPubMed
58.
Schlegel A, Lesurtel M, Melloul E, Limani P, Tschuor C, Graf R, et al. ALPPS: from human to mice highlighting accelerated and novel mechanisms of liver regeneration. Ann Surg. 2014;260(5):839–46.CrossRefPubMed
59.
Wack KE, Ross MA, Zegarra V, Sysko LR, Watkins SC, Stolz DB. Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver. Hepatology. 2001;33(2):363–78.CrossRefPubMed
60.
61.
Lalor PF, Herbert J, Bicknell R, Adams DH. Hepatic sinusoidal endothelium avidly binds platelets in an integrin-dependent manner, leading to platelet and endothelial activation and leukocyte recruitment. Am J Physiol Gastrointest Liver Physiol. 2013;304(5):G469–78.PubMedCentralCrossRefPubMed
62.
Gracia-Sancho J, Maeso-Diaz R, Fernandez-Iglesias A, Navarro-Zornoza M, Bosch J. New cellular and molecular targets for the treatment of portal hypertension. Hepatol Int. 2015;9(2):183–91.CrossRefPubMed
63.
Croner RS, Hoerer E, Kulu Y, Hackert T, Gebhard MM, Herfarth C, et al. Hepatic platelet and leukocyte adherence during endotoxemia. Crit Care. 2006;10(1):R15.PubMedCentralCrossRefPubMed
64.
Kawasaki T, Murata S, Takahashi K, Nozaki R, Ohshiro Y, Ikeda N, et al. Activation of human liver sinusoidal endothelial cell by human platelets induces hepatocyte proliferation. J Hepatol. 2010;53(4):648–54.CrossRefPubMed
65.
Rahbari NN, Garden OJ, Padbury R, Brooke-Smith M, Crawford M, Adam R, et al. Posthepatectomy liver failure: a definition and grading by the International Study Group of Liver Surgery (ISGLS). Surgery. 2011;149(5):713–24.CrossRefPubMed
66.
Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.PubMedCentralCrossRefPubMed
Metadaten
Titel
The role of platelets and portal venous pressure fluctuations in postoperative liver regeneration
verfasst von
P. Starlinger, MD, PhD
A. Assinger
T. Gruenberger
C. Brostjan
Publikationsdatum
01.12.2015
Verlag
Springer Vienna
Erschienen in
European Surgery / Ausgabe 6/2015
Print ISSN: 1682-8631
Elektronische ISSN: 1682-4016
DOI
https://doi.org/10.1007/s10353-015-0352-6

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