{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T22:46:23Z","timestamp":1793486783092,"version":"4.5.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1999,12,14]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Cardiac hypertrophy is a fundamental adaptive response to hemodynamic overload; how mechanical load induces cardiac hypertrophy, however, remains elusive. It was recently reported that activation of a calcium-dependent phosphatase, calcineurin, induces cardiac hypertrophy. In the present study, we examined whether calcineurin plays a critical role in pressure overload\u2013induced cardiac hypertrophy.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Pressure overload produced by constriction of the abdominal aorta increased the activity of calcineurin in the rat heart and induced cardiac hypertrophy, including reprogramming of gene expression. Treatment of rats with a calcineurin inhibitor, FK506, inhibited the activation of calcineurin and prevented the pressure overload\u2013induced cardiac hypertrophy and fibrosis without change of hemodynamic parameters. Load-induced expression of immediate-early-response genes and fetal genes was also suppressed by the FK506 treatment.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The present results suggest that the calcineurin signaling pathway plays a pivotal role in load-induced cardiac hypertrophy and may pave the way for a novel pharmacological approach to prevent cardiac hypertrophy.\n          <\/jats:p>","DOI":"10.1161\/01.cir.100.24.2449","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:42:29Z","timestamp":1339461749000},"page":"2449-2454","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":117,"title":["Calcineurin Plays a Critical Role in Pressure Overload\u2013Induced Cardiac Hypertrophy"],"prefix":"10.1161","volume":"100","author":[{"given":"Masaki","family":"Shimoyama","sequence":"first","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doubun","family":"Hayashi","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiki","family":"Takimoto","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzeng","family":"Zou","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Oka","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Uozumi","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiyo","family":"Kudoh","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futoshi","family":"Shibasaki","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yazaki","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[{"name":"From the Department of Cardiovascular Medicine, University of Tokyo, Graduate School of Medicine (M.S., D.H., E.T., Y.Z., T.O., H.U., S.K., Y.Y., I.K.), and the Tokyo Metropolitan Institute of Medical Science (F.S), Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199001113220206"},{"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.ph.55.030193.000415"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.64.6.2470528"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","unstructured":"Simpson P Bishopric N Coughlin S Karliner J Ordahl C Starksen N Tsao T White N Williams L. Dual trophic effects of the alpha 1-adrenergic receptor in cultured neonatal rat heart muscle cells. J Mol Cell Cardiol. 1986;18(suppl):45\u201358.","DOI":"10.1016\/S0022-2828(86)80460-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.126.6.1565"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(95)00096-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.22.14057"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.10.5423"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950170605"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.15.1.707"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.281.5383.1690"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.62.6.2454761"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.131.3.735"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.89.5.8181146"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.83.6.1828192"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.69.2.1830516"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.84.6.735"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/2578"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.84.6.722"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199410273311702"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90124-H"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90214-3"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.34.20385"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1997.sp022025"},{"key":"e_1_3_2_27_2","first-page":"258","volume":"75","year":"1993","unstructured":"Sadoshima J, Xu Y, Slayter HS, Izumo S. Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell. 1993;75:258\u2013265.","journal-title":"Cell"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3221"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5391.1007a"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.84.6.729"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.82.7.779"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.1142"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.16.2499"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1404"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/6430"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.CIR.100.24.2449","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T13:19:13Z","timestamp":1715519953000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.100.24.2449"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,12,14]]},"references-count":35,"journal-issue":{"issue":"24","published-print":{"date-parts":[[1999,12,14]]}},"alternative-id":["10.1161\/01.CIR.100.24.2449"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.100.24.2449","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,12,14]]},"assertion":[{"value":"1999-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-07-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-12-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}