Abstract
Background and Aims: Portal hypertensive gastropathy (PHG) is now recognized as a distinct entity; however, the angiogenesis in the portal hypertensive gastric mucosa has yet to be elucidated. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor involved in both physiological and pathological angiogenesis. The aim of this study was thus to examine the function of VEGF in the portal hypertensive and non-portal hypertensive gastric mucosa. Method: Forty-five cirrhotic patients were divided into 3 groups as follows. Group I included 15 patients without PHG who were treated with 1.5 g teprenone/day for 8 weeks: PHG(–)-t. Group II included 15 patients with PHG who were not treated with teprenone: PHG(+)-n. Group III included 15 patients with PHG who were treated with teprenone for 8 weeks: PGH(+)-t. The gastric mucosal blood flow (GMBF), the concentration of gastric mucosal VEGF and hexosamine and the endoscopic findings were studied both before and after medication. Results: Before teprenone treatment, the GMBF in the antrum, fundus, fornix were significantly higher in PHG(+)-n than PHG(–)-t. After treatment, the GMBF in the fundus and fornix significantly decreased more than before treatment in the PHG(+)-t. After treatment, the GMBF in the antrum increased significantly more than before treatment in PHG(–)-t. The gastric VEGF and hexoxamine concentration in the antrum were significantly higher in PHG(+)-n than in PHG(–)-t. After treatment, the gastric VEGF and hexosamine concentration in the antrum significantly decreased in PHG(+)-t while no change in concentration was recognized in PHG(+)-n. In the endoscopic findings, a decrease in the PHG score was recognized in 2 patients in PHG(+)-t. Conclusion: Portal hypertensive gastric mucosal change was thus found to trigger a high concentration of VEGF and hexosamine. Such increased activity of VEGF and hexosamine may thus account for the presence of active congestion in PHG.
Journal Section:
Original Paper: Liver
References
1.
McCormack TT, Sims J, Eyre-Book I, et al: Gastric lesions in portal hypertension: Inflammatory gastritis or congestive gastropathy? Gut 1985;26:1226–1232.
[PubMed]
2.
Tanoue K, Hashizume M, Wada H, et al: Effects of endoscopic injection sclerotherapy on portal hypertensive gastropathy; a prospective study. Gastrointest Endosc 1992;38:582–585.
[PubMed]
3.
Ohta M, Hashizume M, Higashi H, et al: Portal and gastric mucosal hemodynamics in cirrhotic patients with portal-hypertensive gastropathy. Hepatology 1994;20:1432–1436.
[PubMed]
4.
Panés J, Bordas JM, Piqué JM, et al: Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy. Gastroenterology 1992;103:1875–1882.
[PubMed]
5.
Kotzampassi K, Eleftheriadis E, Aletras H, et al: Gastric mucosal blood flow in portal hypertensive patients: A laser Doppler flowmetry study. Hepatogastroenterology 1992;39:39–42.
[PubMed]
6.
Guslandi M, Sorghi M, Foppa L, et al: Congestive gastropathy versus chronic gastritis: A comparison of some pathophysiological aspects. Digestion 1993;54:160–162.
[PubMed]
7.
Iwao T, Toyonaga A, Ikegami M, et al: Reduced gastric mucosal blood flow in patients with portal hypertensive gastropathy. Hepatology 1993;18:36–40.
[PubMed]
8.
Hashizume M, Tanaka K, Inokuchi K: Morphology of gastric microcirculation in cirrhosis. Hepatology 1983;3:1008–1012.
[PubMed]
9.
Hashizume M, Kitano S, Sugimachi K, et al: Three-dimensional view of the vascular structure of the lower esophagus in clinical portal hypertension. Hepatology 1988;8:1482–1487.
[PubMed]
10.
Senger DR, Galli SJ, Dvorak AM, et al: Tumor cells secrete a vascular permeability factor that promotes the accumulation of ascites fluid. Science 1983;219:983–985.
[PubMed]
11.
Leung DW, Cachianes G, Kuang WJ, et al: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 1989;246:1306–1309.
[PubMed]
12.
Shibuya M, Yamaguchi S, Yamane A, et al: Nucleotide sequence and expression of a novel human receptor-type tyrosine kinase gene (flt) closely related to the fms family. Oncogene 1990;5:519–524.
[PubMed]
13.
Yamane A, Seetharam L, Yamaguchi S, et al: A new communication system between hepatocytes and sinusoidal endothelial cells in liver through vascular endothelial growth factor and Flt tyrosine kinase receptor family (Flt-1 and KDR/FII-1). Oncogene 1994;9:2683–2690.
[PubMed]
14.
Mise M, Arii S, Higashitsuji H, et al: Clinical significance of vascular endothelial growth factor and basic fibroblast growth factor gene expression in liver tumor. Hepatology 1996;23:455–464.
[PubMed]
15.
Suzuki K, Hayashi N, Miyamoto T, et al: Expression of vascular permeability factor/vascular endothelial growth factor in human hepatocellular carcinoma. Cancer Res 1996;56:3004–3009.
[PubMed]
16.
Shweiki D, Itin A, Soffer D, et al: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992;359:843–845.
[PubMed]
17.
Ladoux A, Frelin C: Hypoxia is a strong inducer of vascular endothelial growth factor mRNA expression in the heart. Biochem Biophys Res Commun 1993;195:1005–1010.
[PubMed]
18.
Isner JM, Pieczek A, Schainfeld R, et al: Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patients with ischaemic limb. Lancet 1996;348:370–374.
[PubMed]
19.
Panés J, Bordas JM, Piqué JM, et al: Increased gastric mucosal perfusion in cirrhotic patients with portal hypertensive gastropathy. Gastroenterology 1992;103:1875–1882.
[PubMed]
20.
Kiel JW, Riedel GI, DiResta GR, et al: Gastric mucosal blood flow measured by laser-Doppler velocimetry. Am J Physiol 1985;249:G539–G545.
[PubMed]
21.
Kvietys RR, Shepherd AP, Granger DN: Laser-Doppler, H2 clearance, and microsphere estimates of mucosal blood flow. Am J Physiol 1985;249:G221–G227.
[PubMed]
22.
Ahn H, Lindhagen J, Nilsson GE, et al: Evaluation of laser Doppler flowmetry in the assessment of intestinal blood flow in cat. Gastroenterology 1985;88:951–957.
[PubMed]
23.
Christoforidis EC, Hovendal C, Bjerring P, et al: Continuous measurement of gastric blood flow by laser-Doppler flowmetry during endoscopy. Scand J Gastroenterol 1989;24:16–20.
[PubMed]
24.
Fujita M, Ikemoto M, Kishishita M, et al: Elevated basic fibroblast growth factor in pericardial fluid of patients with unstable angina. Circulation 1996;94:610–613.
[PubMed]
25.
Neuhaus OW, Letzring M: Determination of hexosamines in conjunction with electrophoresis on starch. Anal Chem 1957;29:1230–1233.
26.
Hashizume M, Sugimachi K: Classification of gastric lesions associated with portal hypertension. J Gastroenterol Hepatol 1995;10:339–343.
[PubMed]
27.
Spina G, Archidiacono R: Gastric Endoscopic Features in Portal Hypertension. Milan, Masson, 1994.
28.
Lamarque D, Levoir D, Duvoux C, et al: Measurement of gastric intramucosal pH in patients with cirrhosis and portal hypertensive gastropathy. Gastroenterol Clin Biol 1994;18:969–974.
[PubMed]
29.
Geraghty JG, Angerson WJ, Carter DC: A study of regional gastric mucosal blood flow in a rat model of hepatic cirrhosis. Am J Physiol 1992;262:G727–G731.
[PubMed]
30.
Kunisaki C, Sugiyama M: Effect of teprenone on acute gastric mucosal lesions induced by cold-restraint stress. Digestion 1992;53:45–53.
[PubMed]
31.
Murakami M, Oketani K, Fujisaki H, et al: Antiulcer effect of geranylgeranylacetone, a new acyclic polyisoprenoid, on experimentally induced gastric and duodenal ulcers in rats. Arzneimittelforschung 1981;31:799–804.
[PubMed]
32.
Terano A, Shiga J, Hiraishi H, et al: Protective action of tetraprenylacetone against ethanol-induced damage in rat gastric mucosa. Digestion 1986;35:182–188.
[PubMed]
33.
Itoh Y, Suzuki K, Matsubara M, et al: Changes in gastric mucosal content of adenosine, xanthine and hypoxanthine induced by restrained water immersion stress: Antiulcer effects of tetraprenylacetone. Digestion 1991;48:25–33.
[PubMed]
34.
Nishizawa Y, Sakurai H, Oketani K, et al: Effects of taurocholic acid/HCl alone or after pretreatment with geranylgeranylacetone on phospholipid metabolism in rat gastric mucosa. Biochem Pharmacol 1987;36:4111–4117.
[PubMed]
35.
Bilski J, Murty VLN, Nadziejko C, et al: Protection against alcohol-induced gastric mucosal injury by geranylgeranylacetone: Effect of indomethacin. Digestion 1988;41:22–23.
[PubMed]
36.
Tarnawski A, Ivey KJ, Stachura J, et al: Protection by prostaglandin against ethanol-induced gastric mucosal damage in man. An endoscopic and histologic assessment (abstract). Gastroenterology 1981;80:1300.
37.
Tarnawski Stachura J, Ivey KJ, et al: Ethanol-induced duodenal lesions in man: Protective effect of prostaglandin. Prostaglandins 1981;21:147–153.
[PubMed]
38.
Tarnawski A, Hollander D, Stachura J, et al: Prostaglandin protection of the gastric mucosa against alcohol injury: A dynamic time-related process. Gastroenterology 1985;88:334–352.
[PubMed]
39.
Lacy ER, Ito S: Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with prostaglandin. Gastroenterology 1982;83:619–625.
[PubMed]
40.
Guth PH, Paulsen G, Nagata H: Histologic and microcirculatory changes in alcohol-induced gastric lesions in the rat: Effect of prostaglandin cytoprotection. Gastroenterology 1984;87:1083–1090.
[PubMed]
41.
Wang JY, Hsieh JS, Huang TJ: Changes in rat gastric mucosal glycoproteins in portal hypertension. Eur Sur Res 1997;29:280–286.
[PubMed]
42.
Ohta Y, Kobayashi T, Nishida K, et al: Relationship between changes of active oxygen metabolism and blood flow and formation, progression, and recovery of lesions is gastric mucosa of rats with a single treatment of compound 48/80, a mast cell degranulator. Dig Dis Sci 1997;42:1221–1232.
[PubMed]
43.
Tanoue K, Tarnawski A, Kishihara F, et al: Effect of teprenone on portal hypertensive gastric mucosa. Digestion 1996;57:35–40.
[PubMed]
44.
Sarfeh IJ, Tarnawski A, Malki A: Portal hypertension and gastric mucosal injury in rats. Gastroenterology 1983;34:987–993.
45.
Tarnawski A, Sarfeh IJ, Stachura J, et al: Microvascular abnormalities of the portal hypertensive gastric mucosa. Hepatology 1988;8:1488–1494.
[PubMed]
46.
Takahashi M, Kawabe T, Ogura K, et al: Expression of vascular endothelial growth factor at the human gastric ulcer margin and in cultured gastric fibroblast: A new angiogenic factor for gastric ulcer. Biochem Biophys Res Commun 1997;234:493–498.
[PubMed]
47.
Ostrow JD: Gastric secretion in human hepatic cirrhosis. Gastroenterology 1960;38:303–313.
48.
Groszmann RJ: Hyperdynamic circulation of liver disease 40 years later: Pathophysiology and clinical consequences. Hepatology 1994;20:1359–1363.
[PubMed]
49.
Takahashi M, Ogura K, Maeda S, et al: Promoters of epithelialization induce expression of vascular endothelial growth factor in human gastric epithelial cells in primary culture. FEBS Lett 1997;418:115–118.
[PubMed]
50.
Nakamura M, Katano M, Fujimoto K, et al: A new prognostic strategy for gastric carcinoma. Ann Surg 1997;226:35–42.
[PubMed]
51.
Shiraishi S, Nakagawa K, Kinukawa K, et al: Immunohistochemical localization of vascular endothelial growth factor in the human placenta. Placenta 1996;17:111–121.
© 2000 S. Karger AG, Basel
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
2000
You do not currently have access to this content.
