58
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The living aortic valve: From molecules to function

      review-article

      Read this article at

      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

          The aortic valve lies in a unique hemodynamic environment, one characterized by a range of stresses (shear stress, bending forces, loading forces and strain) that vary in intensity and direction throughout the cardiac cycle. Yet, despite its changing environment, the aortic valve opens and closes over 100,000 times a day and, in the majority of human beings, will function normally over a lifespan of 70–90 years. Until relatively recently heart valves were considered passive structures that play no active role in the functioning of a valve, or in the maintenance of its integrity and durability. However, through clinical experience and basic research the aortic valve can now be characterized as a living, dynamic organ with the capacity to adapt to its complex mechanical and biomechanical environment through active and passive communication between its constituent parts. The clinical relevance of a living valve substitute in patients requiring aortic valve replacement has been confirmed. This highlights the importance of using tissue engineering to develop heart valve substitutes containing living cells which have the ability to assume the complex functioning of the native valve.

          Related collections

          Most cited references159

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

          Gene regulatory networks in the evolution and development of the heart.

          Eric Olson (2006)
          The heart, an ancient organ and the first to form and function during embryogenesis, evolved by the addition of new structures and functions to a primitive pump. Heart development is controlled by an evolutionarily conserved network of transcription factors that connect signaling pathways with genes for muscle growth, patterning, and contractility. During evolution, this ancestral gene network was expanded through gene duplication and co-option of additional networks. Mutations in components of the cardiac gene network cause congenital heart disease, the most common human birth defect. The consequences of such mutations reveal the logic of organogenesis and the evolutionary origins of morphological complexity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tensegrity: the architectural basis of cellular mechanotransduction.

            D. Ingber (1997)
            Physical forces of gravity, hemodynamic stresses, and movement play a critical role in tissue development. Yet, little is known about how cells convert these mechanical signals into a chemical response. This review attempts to place the potential molecular mediators of mechanotransduction (e.g. stretch-sensitive ion channels, signaling molecules, cytoskeleton, integrins) within the context of the structural complexity of living cells. The model presented relies on recent experimental findings, which suggests that cells use tensegrity architecture for their organization. Tensegrity predicts that cells are hard-wired to respond immediately to mechanical stresses transmitted over cell surface receptors that physically couple the cytoskeleton to extracellular matrix (e.g. integrins) or to other cells (cadherins, selectins, CAMs). Many signal transducing molecules that are activated by cell binding to growth factors and extracellular matrix associate with cytoskeletal scaffolds within focal adhesion complexes. Mechanical signals, therefore, may be integrated with other environmental signals and transduced into a biochemical response through force-dependent changes in scaffold geometry or molecular mechanics. Tensegrity also provides a mechanism to focus mechanical energy on molecular transducers and to orchestrate and tune the cellular response.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology.

              The study of the cellular and molecular pathogenesis of heart valve disease is an emerging area of research made possible by the availability of cultures of valve interstitial cells (VICs) and valve endothelial cells (VECs) and by the design and use of in vitro and in vivo experimental systems that model elements of valve biological and pathobiological activity. VICs are the most common cells in the valve and are distinct from other mesenchymal cell types in other organs. We present a conceptual approach to the investigation of VICs by focusing on VIC phenotype-function relationships. Our review suggests that there are five identifiable phenotypes of VICs that define the current understanding of their cellular and molecular functions. These include embryonic progenitor endothelial/mesenchymal cells, quiescent VICs (qVICs), activated VICs (aVICs), progenitor VICs (pVICs), and osteoblastic VICs (obVICs). Although these may exhibit plasticity and may convert from one form to another, compartmentalizing VIC function into distinct phenotypes is useful in bringing clarity to our understanding of VIC pathobiology. We present a conceptual model that is useful in the design and interpretation of studies on the function of an important phenotype in disease, the activated VIC. We hope this review will inspire members of the investigative pathology community to consider valve pathobiology as an exciting new frontier exploring pathogenesis and discovering new therapeutic targets in cardiovascular diseases.
                Bookmark

                Author and article information

                Journal
                Glob Cardiol Sci Pract
                Glob Cardiol Sci Pract
                GCSP
                GCSP
                Global Cardiology Science & Practice
                Bloomsbury Qatar Foundation Journals (Qatar )
                2305-7823
                2014
                29 January 2014
                : 2014
                : 1
                : 52-77
                Affiliations
                [1] 1National Heart and Lung Institute Imperial College London Heart Science Centre Harefield, UK
                [2] 2Qatar Cardiovascular Research Center Qatar Foundation Doha, Qatar
                [3] 3Montreal Heart Institute Belanger St. East Montreal, Canada
                [4] 4Department of Biomedical Engineering Cornel University Ithaca, NY, USA
                [5] 5Department of Materials Imperial College London London, UK
                Author notes
                Article
                gcsp.2014.11
                10.5339/gcsp.2014.11
                4104380
                25054122
                47316b91-a8dd-4a58-8f80-e1e553715bef
                © 2014 Chester, El-Hamamsy, Butcher, Latif, Bertazzo, Yacoub, licensee Bloomsbury Qatar Foundation Journals.

                This is an open access article distributed under the terms of the Creative Commons Attribution license CC BY 4.0, which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 01 April 2014
                : 28 April 2014
                Categories
                Review Article

                cells,endothelium,nerves,developmental biology,mechanobiology,nanostructure aortic stenosis,calcification

                Comments

                Comment on this article