{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:57:13Z","timestamp":1791093433889,"version":"4.1.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Objective\u2014<\/jats:italic>\n            <\/jats:bold>\n            Impairment of transforming growth factor (TGF)-\u03b21 signaling accelerates atherosclerosis in experimental mice. However, it is uncertain whether increased TGF-\u03b21 expression would retard atherosclerosis. The role of TGF-\u03b21 in aneurysm formation is also controversial. We tested whether overexpression of active TGF-\u03b21 in hyperlipidemic mice affects atherogenesis and aortic dilation.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            We generated apolipoprotein E-null mice with transgenes that allow regulated overexpression of active TGF-\u03b21 in their hearts. Compared to littermate controls, these mice had elevated cardiac and plasma TGF-\u03b21, less aortic root atherosclerosis (\n            <jats:italic>P<\/jats:italic>\n            \u22640.002), fewer lesions in the thoracic and abdominal aortae (\n            <jats:italic>P<\/jats:italic>\n            \u22640.01), less aortic root dilation (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.001), and fewer pseudoaneurysms (\n            <jats:italic>P<\/jats:italic>\n            =0.02). Mechanistic studies revealed no effect of TGF-\u03b21 overexpression on plasma lipids or cytokines, or on peripheral lymphoid organ cells. However, aortae of TGF-\u03b21-overexpressing mice had fewer T-lymphocytes, more collagen, less lipid, lower expression of inflammatory cytokines and matrix metalloproteinase-13, and higher expression of tissue inhibitor of metalloproteinase-2.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            When overexpressed in the heart and plasma, TGF-\u03b21 is an antiatherogenic, vasculoprotective cytokine that limits atherosclerosis and prevents aortic dilation. These actions are associated with significant changes in cellularity, collagen and lipid accumulation, and gene expression in the artery wall.\n          <\/jats:p>","DOI":"10.1161\/atvbaha.109.186593","type":"journal-article","created":{"date-parts":[[2009,3,27]],"date-time":"2009-03-27T01:43:26Z","timestamp":1238118206000},"page":"1251-1257","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["TGF-\u03b21 Limits Plaque Growth, Stabilizes Plaque Structure, and Prevents Aortic Dilation in Apolipoprotein E-Null Mice"],"prefix":"10.1161","volume":"29","author":[{"given":"Andrew D.","family":"Frutkin","sequence":"first","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goro","family":"Otsuka","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"April","family":"Stempien-Otero","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casilde","family":"Sesti","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Du","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mia","family":"Jaffe","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hele\u0301n L.","family":"Dichek","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline J.","family":"Pennington","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan R.","family":"Edwards","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madeline","family":"Nieves-Cintro\u0301n","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Minter","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Preusch","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie Hong","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien C.","family":"Marie","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. Current affiliation for J.C.M.: Inserm U758, Universite\u0301 Claude Bernard Lyon 1, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Dichek","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine (A.D.F., G.O., A.S.-O., C.S., L.D., M.J., D.M., J.H.H., D.A.D.), Pediatrics (H.L.D.), Physiology (M.N.-C.), Pathology (M.P.), and Immunology (J.C.M.), University of Washington School of Medicine, Seattle; and the School of Biological Sciences (C.J.P., D.R.E.), University of East Anglia, Norwich, Norfolk, UK. 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