{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:18:43Z","timestamp":1790255923837,"version":"4.1.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2022,6]]},"abstract":"\n Background:<\/jats:title>\n To test the hypothesis that smooth muscle cell (SMC) TGF-\u03b2 (transforming growth factor beta) signaling contributes to maintenance of aortic structure and function beyond the early postnatal period.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n \n We deleted the TBR2 (type 2 TGF-\u03b2 receptor) in SMC of 11-month-old mice (genotype\n Acta2<\/jats:italic>\n -CreER\n T2+\/0<\/jats:sup>\n Tgfbr2<\/jats:italic>\n f\/f<\/jats:sup>\n , termed TBR2\n SM\u0394<\/jats:sup>\n ) and compared their ascending aorta structure and vasomotor function to controls (\n Acta2<\/jats:italic>\n -CreER\n T20\/0<\/jats:sup>\n Tgfbr2<\/jats:italic>\n f\/f<\/jats:sup>\n , termed TBR2\n f\/f<\/jats:sup>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n \n We confirmed loss of aortic SMC TBR2 by immunoblotting. Four weeks after SMC TBR2 loss, TBR2\n SM\u0394<\/jats:sup>\n mice did not have aortic rupture, ulceration, dissection, dilation, or evidence of medial hemorrhage. However, aortic medial area of TBR2\n SM\u0394<\/jats:sup>\n mice was increased by 27% (0.14\u00b10.01 versus 0.11\u00b10.01 mm\n 2<\/jats:sup>\n ;\n P<\/jats:italic>\n =0.01) and medial thickness was increased by 23% (40\u00b11.9 versus 33\u00b11.3 \u03bcm;\n P<\/jats:italic>\n =0.004) compared with littermate controls. Wire myography performed on ascending aortic rings showed hypercontractility of TBR2\n SM\u0394<\/jats:sup>\n aortas to phenylephrine (E\n max<\/jats:sub>\n , 15.9\u00b11.2 versus 10.8\u00b10.7 mN;\n P<\/jats:italic>\n =0.0003) and reduced relaxation and sensitivity to acetylcholine (E\n max<\/jats:sub>\n , 64\u00b114% versus 96\u00b12%;\n P<\/jats:italic>\n =0.001; \u2212logEC\n 50<\/jats:sub>\n , 6.9\u00b10.1 versus 7.7\u00b10.1;\n P<\/jats:italic>\n =0.0001). Neither maximal relaxation nor sensitivity to sodium nitroprusside differed (E\n max<\/jats:sub>\n , 102\u00b10.3% versus 101\u00b10.3%; \u2212logEC\n 50<\/jats:sub>\n , 8.0\u00b10.04 versus 7.9\u00b10.08;\n P<\/jats:italic>\n >0.4 for both).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n Loss of TGF-\u03b2 signaling in aortic SMC of 1-year-old mice does not cause early severe aortopathy or death; however, it causes mild structural and substantial physiological abnormalities. SMC TGF-\u03b2 signaling plays an important role in maintaining aortic homeostasis in older mice. This role should be considered in the design of clinical studies that aim to prevent aortopathy by blocking SMC TGF-\u03b2 signaling.<\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.122.317603","type":"journal-article","created":{"date-parts":[[2022,4,21]],"date-time":"2022-04-21T05:00:21Z","timestamp":1650517221000},"page":"764-771","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Blockade of TGF-\u03b2 (Transforming Growth Factor Beta) Signaling by Deletion of\n Tgfbr2<\/i>\n in Smooth Muscle Cells of 11-Month-Old Mice Alters Aortic Structure and Causes Vasomotor Dysfunction\u2014Brief Report"],"prefix":"10.1161","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5880-6635","authenticated-orcid":true,"given":"Chloe Y.","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medicine (C.Y.L., S.N.A., L.B., N.S., I.A.Y., D.A.D.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyan N.","family":"Angelov","sequence":"additional","affiliation":[{"name":"Department of Medicine (C.Y.L., S.N.A., L.B., N.S., I.A.Y., D.A.D.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6812-1082","authenticated-orcid":true,"given":"Jay","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery (J.Z.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianxiang","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Medicine (C.Y.L., S.N.A., L.B., N.S., I.A.Y., D.A.D.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6038-2379","authenticated-orcid":true,"given":"Nicole","family":"Sanford","sequence":"additional","affiliation":[{"name":"Department of Medicine (C.Y.L., S.N.A., L.B., N.S., I.A.Y., D.A.D.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5695-5269","authenticated-orcid":true,"given":"Ilkay","family":"Alp Yildirim","sequence":"additional","affiliation":[{"name":"Department of Medicine (C.Y.L., S.N.A., L.B., N.S., I.A.Y., D.A.D.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-2736","authenticated-orcid":true,"given":"David A.","family":"Dichek","sequence":"additional","affiliation":[{"name":"Department of Medicine (C.Y.L., S.N.A., L.B., N.S., I.A.Y., D.A.D.), University of Washington School of Medicine, Seattle."},{"name":"Institute for Stem Cell and Regenerative Medicine\u201a Department of Laboratory Medicine and Pathology (D.A.D.), University of Washington School of Medicine, Seattle."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2006.06.067"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.013169"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11248-010-9379-4"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.238410"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.115.306573"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69942"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep35444"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.315878"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a022269"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v100.2.560"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20448"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.004968"},{"key":"e_1_3_3_14_2","unstructured":"Deleted 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Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.122.317603","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T19:51:11Z","timestamp":1715543471000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.122.317603"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,6]]}},"alternative-id":["10.1161\/ATVBAHA.122.317603"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.122.317603","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"2020-08-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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