{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:28:45Z","timestamp":1790375325115,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,6,9]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Mutations in\n              <jats:italic>ACTA2<\/jats:italic>\n              , encoding the smooth muscle isoform of \u03b1-actin, cause thoracic aortic aneurysms, acute aortic dissections, and occlusive vascular diseases.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We sought to identify the mechanism by which loss of smooth muscle \u03b1-actin causes aortic disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              <jats:italic>Acta2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice have an increased number of elastic lamellae in the ascending aorta and progressive aortic root dilation as assessed by echocardiography that can be attenuated by treatment with losartan, an angiotensin II (AngII) type 1 receptor blocker. AngII levels are not increased in\n              <jats:italic>Acta2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              aortas or kidneys. Aortic tissue and explanted smooth muscle cells from\n              <jats:italic>Acta2<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              aortas show increased production of reactive oxygen species and increased basal nuclear factor \u03baB signaling, leading to an increase in the expression of the AngII receptor type I a and activation of signaling at 100-fold lower levels of AngII in the mutant compared with wild-type cells. Furthermore, disruption of smooth muscle \u03b1-actin filaments in wild-type smooth muscle cells by various mechanisms activates nuclear factor \u03baB signaling and increases expression of AngII receptor type I a.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>These findings reveal that disruption of smooth muscle \u03b1-actin filaments in smooth muscle cells increases reactive oxygen species levels, activates nuclear factor \u03baB signaling, and increases AngII receptor type I a expression, thus potentiating AngII signaling in vascular smooth muscle cells without an increase in the exogenous levels of AngII.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.117.310563","type":"journal-article","created":{"date-parts":[[2017,5,2]],"date-time":"2017-05-02T00:30:33Z","timestamp":1493685033000},"page":"1903-1915","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":58,"title":["Loss of Smooth Muscle \u03b1-Actin Leads to NF-\u03baB\u2013Dependent Increased Sensitivity to Angiotensin II in Smooth Muscle Cells and Aortic Enlargement"],"prefix":"10.1161","volume":"120","author":[{"given":"Jiyuan","family":"Chen","sequence":"first","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Peters","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina L.","family":"Papke","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Villamizar","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea-Jeanne","family":"Ringuette","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiumei","family":"Cao","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangtao","family":"Ma","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limin","family":"Gong","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina L.","family":"Byanova","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Xiong","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael X.","family":"Zhu","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalinda","family":"Madonna","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Kee","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Jian","family":"Geng","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan R.","family":"Brasier","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; Anatomy and Cell Biology, Strathcona Anatomy and Dentistry Building, 3640 Rue University, Montreal, Quebec, Canada; and Internal Medicine, Institute for Translational Sciences, and Sealy Center for Molecular Medicine, University of Texas Medical..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine C.","family":"Davis","sequence":"additional","affiliation":[{"name":"From the Departments of Internal Medicine (J.C., A.P., C.L.P., C.V., J.C., S.W., S.M., L.G., K.L.B., R.M., P.K., Y.-J.G., S.P., C.S.K., D.M.M.) and Integrative Biology and Pharmacology (J.X., M.X.Z.), The University of Texas Health Science Center at Houston; 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