Abstract
Consistent clinical and experimental evidence points to the involvement of two enzymatic systems (the matrix metalloproteinases-MMPs and the protein crosslinking enzymes transglutaminases) in prominent physiologic roles of endothelium in the maintenance of vascular wall integrity, regulation of blood flow and clotting, and exchange of molecules and cells between the extra- and the intravascular space. These issues are briefly discussed in relation to differentiation of the endothelium within the vascular system, mechanisms of molecular regulation and the effects of their disruption in pathology. While the roles of MMPs are now understood in detail and represent a promising target for pharmacological interventions, much less is known on the roles of transglutaminases in vascular biology. These last enzymes are expressed at extremely high levels in endothelial cells and are involved in cell matrix interactions important to angiogenesis and apoptosis/cell death of endothelial cells, in the control of blood clotting and and in the transfer of molecules and cells across the vascular walls. On the clinical side, these properties are relevant in vascular inflammatory processes, atherosclerosis and tumor metastasis. We summarise the large body of evidence available in this perspective and discuss its implications for the development of new therapeutic strategies.
Keywords: endothelium, extracellular matrix, transglutaminases, atherosclerosis, tumor metastasis
Current Medicinal Chemistry
Title: Transglutaminase and Vascular Biology: Physiopathologic Implications and Perspectives for Therapeutic Interventions
Volume: 12 Issue: 20
Author(s): Carlo M. Bergamini, Martin Griffin and Francesco S. Pansini
Affiliation:
Keywords: endothelium, extracellular matrix, transglutaminases, atherosclerosis, tumor metastasis
Abstract: Consistent clinical and experimental evidence points to the involvement of two enzymatic systems (the matrix metalloproteinases-MMPs and the protein crosslinking enzymes transglutaminases) in prominent physiologic roles of endothelium in the maintenance of vascular wall integrity, regulation of blood flow and clotting, and exchange of molecules and cells between the extra- and the intravascular space. These issues are briefly discussed in relation to differentiation of the endothelium within the vascular system, mechanisms of molecular regulation and the effects of their disruption in pathology. While the roles of MMPs are now understood in detail and represent a promising target for pharmacological interventions, much less is known on the roles of transglutaminases in vascular biology. These last enzymes are expressed at extremely high levels in endothelial cells and are involved in cell matrix interactions important to angiogenesis and apoptosis/cell death of endothelial cells, in the control of blood clotting and and in the transfer of molecules and cells across the vascular walls. On the clinical side, these properties are relevant in vascular inflammatory processes, atherosclerosis and tumor metastasis. We summarise the large body of evidence available in this perspective and discuss its implications for the development of new therapeutic strategies.
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Cite this article as:
Bergamini M. Carlo, Griffin Martin and Pansini S. Francesco, Transglutaminase and Vascular Biology: Physiopathologic Implications and Perspectives for Therapeutic Interventions, Current Medicinal Chemistry 2005; 12 (20) . https://dx.doi.org/10.2174/0929867054864804
DOI https://dx.doi.org/10.2174/0929867054864804 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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