{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:11:51Z","timestamp":1790802711884,"version":"4.1.0"},"reference-count":26,"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":[[2011,6,21]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Calcineurin is a calcium-regulated phosphatase that plays a major role in cardiac hypertrophy. We previously described that alternative splicing of the calcineurin A\u03b2 (CnA\u03b2) gene generates the CnA\u03b21 isoform, with a unique C-terminal region that is different from the autoinhibitory domain present in all other CnA isoforms. In skeletal muscle, CnA\u03b21 is necessary for myoblast proliferation and stimulates regeneration, reducing fibrosis and accelerating the resolution of inflammation. Its role in the heart is currently unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>We generated transgenic mice overexpressing CnA\u03b21 in postnatal cardiomyocytes under the control of the \u03b1-myosin heavy chain promoter. In contrast to previous studies using an artificially truncated calcineurin, CnA\u03b21 overexpression did not induce cardiac hypertrophy. Moreover, transgenic mice showed improved cardiac function and reduced scar formation after myocardial infarction, with reduced neutrophil and macrophage infiltration and decreased expression of proinflammatory cytokines. Immunoprecipitation and Western blot analysis showed interaction of CnA\u03b21 with the mTOR complex 2 and activation of the Akt\/SGK cardioprotective pathway in a PI3K-independent manner. In addition, gene expression profiling revealed that CnA\u03b21 activated the transcription factor ATF4 downstream of the Akt\/mTOR pathway to promote the amino acid biosynthesis program, to reduce protein catabolism, and to induce the antifibrotic and antiinflammatory factor growth differentiation factor 15, which protects the heart through Akt activation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Calcineurin A\u03b21 shows a unique mode of action that improves cardiac function after myocardial infarction, activating different cardioprotective pathways without inducing maladaptive hypertrophy. These features make CnA\u03b21 an attractive candidate for the development of future therapeutic approaches.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.110.012211","type":"journal-article","created":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T04:35:51Z","timestamp":1306902951000},"page":"2838-2847","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Calcineurin Splicing Variant Calcineurin A\u03b21 Improves Cardiac Function After Myocardial Infarction Without Inducing Hypertrophy"],"prefix":"10.1161","volume":"123","author":[{"given":"Leanne E.","family":"Felkin","sequence":"first","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Narita","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9e","family":"Germack","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasunori","family":"Shintani","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunihiko","family":"Takahashi","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Padmini","family":"Sarathchandra","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina M.","family":"L\u00f3pez-Ola\u00f1eta","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas M.","family":"G\u00f3mez-Salinero","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Suzuki","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.R.","family":"Barton","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Rosenthal","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Lara-Pezzi","sequence":"additional","affiliation":[{"name":"From the Heart Science Centre, National Heart and Lung Institute, Imperial College London, London, UK (L.E.F., R.G., P.S., K.S., P.J.R.B., N.R., E.L.-P.); Translational Cardiovascular Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK (T.N., Y.S., K.T., K.S.); Mouse Biology Unit, European Molecular Biology Laboratory, Rome, Italy (N.R.); Cardiovascular Development Biology Department, Centro Nacional de..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2003.10.008"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000109415.17511.18"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.072647999"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.041614798"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.86.3.255"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000107197.99679.77"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200704179"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0151"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.02.009"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2501"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M611723200"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.05.008"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M610510200"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI42106"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6252fje"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.4.309"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.107.148791"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000160352.58142.06"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24682"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.172882"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000202804.84885.d0"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000202805.73038.48"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.109.206607"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00105-9"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2009.10.012"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.110.012211","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:16:18Z","timestamp":1715580978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.110.012211"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,21]]},"references-count":26,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2011,6,21]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.110.012211"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.110.012211","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,6,21]]},"assertion":[{"value":"2010-08-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-04-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-05-31","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}