title: Activation of extracellular transglutaminase 2 by mechanical force in the arterial wall.
abstract: Inward remodeling of small arteries occurs after prolonged vasoconstriction, low blood flow, and in several models of hypertension. The cross-linking enzyme, transglutaminases 2 (TG2), is able to induce inward remodeling and stiffening of arteries. The activity of TG2 is dependent on its conformation, which can be open or closed, and on its redox state. Several factors have been shown to be involved in modulating TG2 activity, including Ca(2+) and GTP/GDP concentrations, as well as the redox state of the environment. This review introduces the hypothesis that mechanical force could be involved in regulating the activity of TG2 during inward remodeling by promoting its open and reduced active state. Several aspects of TG2, such as its structure and localization, are assessed in order to provide arguments that support the hypothesis. We conclude that a direct activation of TG2 by mechanical force exerted by smooth muscle cells may explain the link between smooth muscle activation and inward remodeling, as observed in several physiological and pathological conditions.
authors.affiliation: Department of Biomedical Engineering and Physics, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Guizela
authors.initials: G
authors.lastname: Huelsz-Prince
authors.forename: Alexey M
authors.initials: AM
authors.lastname: Belkin
authors.forename: Ed
authors.initials: E
authors.lastname: VanBavel
authors.forename: Erik N T P
authors.initials: EN
authors.lastname: Bakker
mesh_terms: D000818:Animals; D001158:Arteries / Q000201:enzymology* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D004220:Disulfides / Q000378:metabolism; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D039081:Integrin alpha5beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology; D011487:Protein Conformation / Q000187:drug effects; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013314:Stress, Mechanical; D016608:Talin / Q000378:metabolism; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D016596:Vinculin / Q000378:metabolism
chemical_list: D004220:Disulfides; D005353:Fibronectins; D039081:Integrin alpha5beta1; D016023:Integrins; D016608:Talin; D016596:Vinculin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium