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      Morphologic, Phenotypic and Functional Characteristics of Endothelial Cells Derived from Human Hepatic Cavernous Hemangioma

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          Abstract

          Backgrounds/Aims: The pathogenesis of cavernous hemangiomas is largely unknown, and it is speculated that abnormal vasculogenesis and angiogenesis may be involved. In this study, the characteristics of cavernous hemangioma endothelial cells (CHECs) derived from the human liver were analyzed in terms of morphology, phenotype and function and compared with human liver sinusoidal endothelial cells (LSECs). Methods and Results: By transmission electron microscopy, abnormally expanded endoplasmic reticulum (ER) and similarly arranged cytoplasmic vacuoles were only found in CHECs. Phenotypic analysis showed that the expression of αvβ3 was significantly increased in CHECs. mRNA expression of vascular endothelial growth factor A, and angiopoietins 1 and 2 was significantly increased in CHECs compared to LSECs. The functional analysis indicated that CHECs released more vascular endothelial growth factor A, produced significantly more pro-matrix metalloproteinase 2 (pro-MMP2) and activated MMP2, and exhibited higher procoagulant and fibrinolytic activities compared with LSECs. Confocal microscopy revealed that MMP2 was concentrated in some cytoplasmic granules of CHECs and was consistent with the distribution of expanded ER. CHECs exhibited more activated angiogenesis capacity and formed abnormal capillary-like structures in vitro. Conclusion: These results suggested that endothelial cells (ECs) derived from human cavernous hemangiomas differ from normal ECs in morphology, phenotype and function.

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          Vascular-specific growth factors and blood vessel formation.

          G Yancopoulos, S. Davis, N W Gale … (2000)
          A recent explosion in newly discovered vascular growth factors has coincided with exploitation of powerful new genetic approaches for studying vascular development. An emerging rule is that all of these factors must be used in perfect harmony to form functional vessels. These new findings also demand re-evaluation of therapeutic efforts aimed at regulating blood vessel growth in ischaemia, cancer and other pathological settings.
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            Matrix metalloproteinases in angiogenesis: a moving target for therapeutic intervention.

            Dennis W Stevenson (1999)
            Article 0 comments Cited 133 times – based on 0 reviews     Review now
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              Cellular markers that distinguish the phases of hemangioma during infancy and childhood.

              John Mulliken, J Folkman, H Kozakewich … (1994)
              Hemangiomas, localized tumors of blood vessels, appear in approximately 10-12% of Caucasian infants. These lesions are characterized by a rapid proliferation of capillaries for the first year (proliferating phase), followed by slow, inevitable, regression of the tumor over the ensuing 1-5 yr (involuting phase), and continual improvement until 6-12 yr of age (involuted phase). To delineate the clinically observed growth phases of hemangiomas at a cellular level, we undertook an immunohistochemical analysis using nine independent markers. The proliferating phase was defined by high expression of proliferating cell nuclear antigen, type IV collagenase, and vascular endothelial growth factor. Elevated expression of the tissue inhibitor of metalloproteinase, TIMP 1, an inhibitor of new blood vessel formation, was observed exclusively in the involuting phase. High expression of basic fibroblast growth factor (bFGF) and urokinase was present in the proliferating and involuting phases. There was coexpression of bFGF and endothelial phenotypic markers CD31 and von Willebrand factor in the proliferating phase. These results provide an objective basis for staging hemangiomas and may be used to evaluate pharmacological agents, such as corticosteroids and interferon alfa-2a, which accelerate regression of hemangiomas. By contrast, vascular malformations do not express proliferating cell nuclear antigen, vascular endothelial growth factor, bFGF, type IV collagenase, and urokinase. These data demonstrate immunohistochemical differences between proliferating hemangiomas and vascular malformations which reflect the biological distinctions between these vascular lesions.
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                Author and article information

                Journal
                Journal ID (publisher-id): JVR
                Journal ID (nlm-ta): J Vasc Res
                Journal ID (doi): 10.1159/issn.1018-1172
                Title: Journal of Vascular Research
                Publisher: S. Karger AG
                ISSN (Print): 1018-1172
                ISSN (Electronic): 1423-0135
                Publication date Subscription-year: 2006
                Publication date (Print): November 2006
                Publication date (Electronic): 03 November 2006
                Volume: 43
                Issue: 6
                Pages: 522-532
                Affiliations
                aInstitute of Basic Medical Sciences, Peking Union Medical College, bInstitute of Clinical Medical Sciences, China-Japan Friendship Hospital, cDepartment of Endocrinology, Peking Union Hospital, and dCancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking, People‘s Republic of China; eDepartment of Pathology, K25, Faculty of Medicine, University of Sydney, Sydney, Australia
                Article
                Publisher ID: 95965 Other ID: J Vasc Res 2006;43:522–532
                DOI: 10.1159/000095965
                PubMed ID: 17008795
                SO-VID: ba874c89-59a7-4dc8-a0e1-b2dad68a50c1
                Copyright © © 2006 S. Karger AG, Basel
                License:

                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.

                History
                Date received : 05 April 2006
                Date accepted : 05 August 2006
                Page count
                Figures: 8, Tables: 1, References: 27, Pages: 11
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: General medicine,Neurology,Cardiovascular Medicine,Internal medicine,Nephrology
                Keywords: Endothelial cells,Cavernous hemangioma,Hemangioma,Angiogenesis,Phenotype
                Data availability:
                ScienceOpen disciplines: General medicine, Neurology, Cardiovascular Medicine, Internal medicine, Nephrology
                Keywords: Endothelial cells, Cavernous hemangioma, Hemangioma, Angiogenesis, Phenotype

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