{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:33:26Z","timestamp":1791178406239,"version":"4.1.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:p>\n            The hypertrophic response of the heart has been recognized recently as the net result of activation of prohypertrophic and antihypertrophic pathways. Here we report the involvement of the Wnt\/Frizzled pathway in the onset of cardiac hypertrophy development. Stimulation of the Wnt\/Frizzled pathway activates the disheveled (Dvl) protein. Disheveled subsequently can inhibit glycogen synthase kinase-3\u03b2, a protein with potent antihypertrophic actions through diverse molecular mechanisms. In the Wnt\/Frizzled pathway, inhibition of glycogen synthase kinase-3\u03b2 leads to an increased amount of \u03b2-catenin, which can act as a transcription factor for several hypertrophy-associated target genes. In this study we subjected mice lacking the\n            <jats:italic>Dvl-1<\/jats:italic>\n            gene and their wild-type littermates to thoracic aortic constriction for 7, 14, and 35 days. In mice lacking the\n            <jats:italic>Dvl-1<\/jats:italic>\n            gene, 7 days of pressure overload-induced increases in left ventricular posterior wall thickness and expression of atrial natriuretic factor and brain natriuretic protein were attenuated compared with their wild-type littermates. \u03b2-Catenin protein amount was reduced in the group lacking the\n            <jats:italic>Dvl-1<\/jats:italic>\n            gene, and an increased glycogen synthase kinase-3\u03b2 activity was observed. Moreover, the increase in the amount of Ser\n            <jats:sup>473<\/jats:sup>\n            -phosphorylated Akt, a stimulator of cardiac hypertrophy, was lower in the group lacking the\n            <jats:italic>Dvl-1<\/jats:italic>\n            gene. In conclusion, we have demonstrated that interruption of Wnt signaling in the mice lacking the\n            <jats:italic>Dvl-1<\/jats:italic>\n            gene attenuates the onset of pressure overload-induced cardiac hypertrophy through mechanisms involving glycogen synthase kinase-3\u03b2 and Akt. Therefore, the Wnt\/Frizzled pathway may provide novel therapeutic targets for antihypertrophic therapy.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.0000255946.55091.24","type":"journal-article","created":{"date-parts":[[2007,1,9]],"date-time":"2007-01-09T01:39:02Z","timestamp":1168306742000},"page":"473-480","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":99,"title":["Interruption of Wnt Signaling Attenuates the Onset of Pressure Overload-Induced Cardiac Hypertrophy"],"prefix":"10.1161","volume":"49","author":[{"given":"Veerle A.M.","family":"van de Schans","sequence":"first","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne W.M.","family":"van den Borne","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka E.","family":"Strzelecka","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben J.A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos L.J.","family":"van der Velden","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon C.J.","family":"Langen","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antony","family":"Wynshaw-Boris","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos F.M.","family":"Smits","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Matthijs","family":"Blankesteijn","sequence":"additional","affiliation":[{"name":"From the Department of Pharmacology and Toxicology (V.A.M.v.d.S., S.W.M.v.d.B., A.E.S., B.J.A.J., J.F.M.S., W.M.B.), Cardiovascular Research Institute Maastricht, Department of Respiratory Medicine (J.L.J.v.d.V., R.C.J.L.), Maastricht University, Maastricht, the Netherlands; and Howard Hughes Medical Institute (A.W.-B.), University of California, San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.06.012"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199005313222203"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.63.1.391"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.03.015"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000018952.70505.f1"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/35096075"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00384"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.103.5.670"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.151.1.117"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13779"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231619298"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.68.247"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.19.14466"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M103166200"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3290209"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1094291"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1999.1860"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2001.0317"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80354-2"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.104.12.1419"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0109"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2002.0869"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2004.06.020"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0835895100"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600633"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000870200"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64856-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0041-008X(03)00170-4"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/18884"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1603"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/1050-1738(92)90046-U"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.55.030193.000453"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.04.002"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000124977.59827.80"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C000880200"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.0000255946.55091.24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:36:13Z","timestamp":1715531773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.0000255946.55091.24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,3]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2007,3]]}},"alternative-id":["10.1161\/01.HYP.0000255946.55091.24"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.0000255946.55091.24","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,3]]},"assertion":[{"value":"2006-05-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-12-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2007-01-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}