2
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found

      Transforming Growth Factor-β Signaling in Thoracic Aortic Aneurysm Development: A Paradox in Pathogenesis

      Read this article at

      ScienceOpenPublisherPMCPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behavior, pose a serious health risk characterized by the lack of medical treatment options and high rates of surgical morbidity and mortality. Independent of the inciting stimuli (biochemical/mechanical), TAA development proceeds by a multifactorial process influenced by both cellular and extracellular mechanisms, resulting in alterations of the structure and composition of the vascular extracellular matrix (ECM). While the role of enhanced ECM proteolysis in TAA formation remains undisputed, little attention has been focused on the upstream signaling events that drive the remodeling process. Recent evidence highlighting the dysregulation of transforming growth factor-β (TGF-β) signaling in ascending TAAs from Marfan syndrome patients has stimulated an interest in this intracellular signaling pathway. However, paradoxical discoveries have implicated both enhanced TGF-β signaling and loss of function TGF-β receptor mutations, in aneurysm formation; obfuscating a clear functional role for TGF-β in aneurysm development. In an effort to elucidate this subject, TGF-β signaling and its role in vascular remodeling and pathology will be reviewed, with the aim of identifying potential mechanisms of how TGF-β signaling may contribute to the formation and progression of TAA.

          Related collections

          Most cited references 119

          • Record: found
          • Abstract: found
          • Article: not found

          Making sense of latent TGFbeta activation.

          TGFbeta is secreted as part of a latent complex that is targeted to the extracellular matrix. A variety of molecules, 'TGFbeta activators,' release TGFbeta from its latent state. The unusual temporal discontinuity of TGFbeta synthesis and action and the panoply of TGFbeta effects contribute to the interest in TGF-beta. However, the logical connections between TGFbeta synthesis, storage and action are obscure. We consider the latent TGFbeta complex as an extracellular sensor in which the TGFbeta propeptide functions as the detector, latent-TGFbeta-binding protein (LTBP) functions as the localizer, and TGF-beta functions as the effector. Such a view provides a logical continuity for various aspects of TGFbeta biology and allows us to appreciate TGFbeta biology from a new perspective.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Mechanisms of TGF-β Signaling from Cell Membrane to the Nucleus

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              How cells read TGF-beta signals.

               J Massagué (2000)
              Cell proliferation, differentiation and death are controlled by a multitude of cell-cell signals, and loss of this control has devastating consequences. Prominent among these regulatory signals is the transforming growth factor-beta (TGF-beta) family of cytokines, which can trigger a bewildering diversity of responses, depending on the genetic makeup and environment of the target cell. What are the networks of cell-specific molecules that mould the TGF-beta response to each cell's needs?
                Bookmark

                Author and article information

                Journal
                JVR
                J Vasc Res
                10.1159/issn.1018-1172
                Journal of Vascular Research
                S. Karger AG
                1018-1172
                1423-0135
                2009
                February 2009
                02 September 2008
                : 46
                : 2
                : 119-137
                Affiliations
                aDepartment of Surgery, Division of Cardiothoracic Surgery Research, Medical University of South Carolina, and bRalph H. Johnson Veterans Affairs Medical Center, Charleston, S.C., USA
                Article
                151766 PMC2645475 J Vasc Res 2009;46:119–137
                10.1159/000151766
                PMC2645475
                18765947
                © 2008 S. Karger AG, Basel

                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.

                Page count
                Figures: 6, Tables: 2, References: 182, Pages: 19
                Categories
                Review

                Comments

                Comment on this article