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In this study, we examined the crosslinking\u2010dependent and crosslinking\u2010independent roles of tissue transglutaminase (\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2) in vascular function and stiffness.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n              s were isolated from the aortae of\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2\u2212\/\u2212 and wild\u2010type (\n              <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n              ) mice. Cell adhesion was examined by using electrical cell\u2013substrate impedance sensing and PicoGreen assay. Cell motility was examined using a Boyden chamber assay. Cell proliferation was examined by electrical cell\u2013substrate impedance sensing and EdU incorporation assays. Cell micromechanics were studied using magnetic torsion cytometry and spontaneous nanobead tracer motions. Aortic mechanics were examined by tensile testing. Vasoreactivity was studied by wire myography.\n              <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n              s from\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2\u2212\/\u2212 mice had delayed adhesion, reduced motility, and accelerated de\u2010adhesion and proliferation rates compared with those from\n              <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n              .\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2\u2212\/\u2212\n              <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n              s were stiffer and displayed fewer cytoskeletal remodeling events than\n              <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n              . Collagen assembly was delayed in\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2\u2212\/\u2212\n              <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n              s and recovered with adenoviral transduction of\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2. Aortic rings from\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2\u2212\/\u2212 mice were less stiff than those from\n              <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n              ; stiffness was partly recovered by incubation with guinea pig liver\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2 independent of crosslinking function.\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2\u2212\/\u2212 rings showed augmented response to phenylephrine\u2010mediated vasoconstriction when compared with\n              <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n              . In human coronary arteries, vascular media and plaque, high abundance of fibronectin expression, and colocalization with\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2 were observed.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">TG<\/jats:styled-content>\n              2 modulates vascular function\/tone by altering\n              <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n              contractility independent of its crosslinking function and contributes to vascular stiffness by regulating\n              <jats:styled-content style=\"fixed-case\">SMC<\/jats:styled-content>\n              proliferation and matrix remodeling.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.004161","type":"journal-article","created":{"date-parts":[[2017,2,4]],"date-time":"2017-02-04T01:10:44Z","timestamp":1486170644000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":68,"title":["Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking\u2010Dependent and Crosslinking\u2010Independent Functions"],"prefix":"10.1161","volume":"6","author":[{"given":"Jochen","family":"Steppan","sequence":"first","affiliation":[{"name":"Department of Anesthesiology &amp; 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