{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:06:59Z","timestamp":1789776419279,"version":"4.0.1"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2013,4,26]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>The adult heart is composed primarily of terminally differentiated, mature cardiomyocytes that express signature genes related to contraction. In response to mechanical or pathological stress, the heart undergoes hypertrophic growth, a process defined as an increase in cardiomyocyte cell size without an increase in cell number. However, the molecular mechanism of cardiac hypertrophy is not fully understood.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To identify and characterize microRNAs that regulate cardiac hypertrophy and remodeling.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Screening for muscle-expressed microRNAs that are dynamically regulated during muscle differentiation and hypertrophy identified microRNA-22 (miR-22) as a cardiac- and skeletal muscle\u2013enriched microRNA that is upregulated during myocyte differentiation and cardiomyocyte hypertrophy. Overexpression of miR-22 was sufficient to induce cardiomyocyte hypertrophy. We generated mouse models with global and cardiac-specific miR-22 deletion, and we found that cardiac miR-22 was essential for hypertrophic cardiac growth in response to stress. miR-22\u2013null hearts blunted cardiac hypertrophy and cardiac remodeling in response to 2 independent stressors: isoproterenol infusion and an activated calcineurin transgene. Loss of miR-22 sensitized mice to the development of dilated cardiomyopathy under stress conditions. We identified Sirt1 and Hdac4 as miR-22 targets in the heart.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Our studies uncover miR-22 as a critical regulator of cardiomyocyte hypertrophy and cardiac remodeling.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.112.300682","type":"journal-article","created":{"date-parts":[[2013,3,23]],"date-time":"2013-03-23T05:33:09Z","timestamp":1364016789000},"page":"1234-1243","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":259,"title":["MicroRNA-22 Regulates Cardiac Hypertrophy and Remodeling in Response to Stress"],"prefix":"10.1161","volume":"112","author":[{"given":"Zhan-Peng","family":"Huang","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghai","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Young","family":"Seok","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Kataoka","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Hu","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Zhi","family":"Wang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Boston Children\u2019s Hospital, Harvard Medical School, Boston, MA (Z.-P.H., J.C., H.Y.S., Z.Z., M.K., X.H.,D.-Z.W.); Department of Cell Biology and Genetics, Chongqing Medical University, Chongqing, China (Z.Z.); and Harvard Stem Cell Institute, Harvard University Cambridge, Cambridge, MA (D.-Z.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-387786-4.00009-9"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1132292"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genom.6.080604.162132"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31044"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra072139"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00242-2"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2008.01.007"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.10.013"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1139089"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature09783"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1725"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI36154"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.041723"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.241"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201010100"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22852"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.044354"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2007.04.004"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5860"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI58227"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19137"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi060641s"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81573-1"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/35040593"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)00025-3"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01875-08"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2010.07594.x"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605895"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.112.300682","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:49:56Z","timestamp":1715572196000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.112.300682"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,26]]},"references-count":28,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2013,4,26]]}},"alternative-id":["10.1161\/CIRCRESAHA.112.300682"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.112.300682","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,26]]},"assertion":[{"value":"2012-12-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-03-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-03-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}