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However, it is not known whether ROCK2 plays an important role in the development of cardiac hypertrophy. To determine whether the loss of ROCK2 could prevent cardiac hypertrophy, cardiomyocyte\u2010specific ROCK2\u2010null (\n                    <jats:italic>\n                      c\u2010ROCK2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) were generated using conditional\n                    <jats:italic>\n                      ROCK2\n                      <jats:sup>flox\/flox<\/jats:sup>\n                    <\/jats:italic>\n                    mice and \u03b1\u2010myosin heavy\u2010chain promoter\u2010driven Cre recombinase transgenic mice. Cardiac hypertrophy was induced by Ang II infusion (400 ng\/kg\/min, 28 d) or transverse aortic constriction (TAC). Under basal conditions, hemodynamic parameters, cardiac anatomy, and function of\n                    <jats:italic>\n                      c\u2010ROCK2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice were comparable to wild\u2010type (WT) mice. However, following Ang II infusion or TAC,\n                    <jats:italic>\n                      c\u2010ROCK2\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice exhibited a substantially smaller increase in heart\u2010to\u2010body weight ratio, left ventricular mass, myocyte cross\u2010sectional area, hypertrophy\u2010related fetal gene expression, intraventricular fibrosis, cardiac apoptosis, and oxidative stress compared to control mice. Deletion of\n                    <jats:italic>ROCK2<\/jats:italic>\n                    in cardiomyocytes leads to increased expression of four\u2010and\u2010a\u2010half LIM\u2010only protein\u20102 (FHL2) and FHL2\u2010mediated inhibition of serum response factor (SRF) and extracellular signal\u2010regulated mitogen\u2010activated protein kinase (ERK). Knockdown of FHL2 expression in ROCK2\u2010deficient cardiomyocytes or placing ROCK2\u2010hap\u2010loinsufficient (\n                    <jats:italic>\n                      ROCK2\n                      <jats:sup>+\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    ) mice on FHL2\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    \u2010haploinsufficient background restored the hypertrophic response to Ang II. These results indicate that cardiomyocyte ROCK2 is essential for the development of cardiac hypertrophy and that up\u2010regulation of FHL2 may contribute to the antihypertrophic phenotype that is observed in cardiac\u2010specific ROCK2\u2010deficient mice.\u2014Okamoto, R., Li, Y., Noma, K., Hiroi, Y., Liu, P.\u2010Y., Taniguchi, M., Ito, M., Liao, J. K. FHL2 prevents cardiac hypertrophy in mice with cardiac\u2010specific deletion of ROCK2.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 1439\u20131449 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-217018","type":"journal-article","created":{"date-parts":[[2012,12,27]],"date-time":"2012-12-27T21:12:22Z","timestamp":1356642742000},"page":"1439-1449","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["FHL2 prevents cardiac hypertrophy in mice with cardiac\u2010specific deletion of ROCK2"],"prefix":"10.1096","volume":"27","author":[{"given":"Ryuji","family":"Okamoto","sequence":"first","affiliation":[{"name":"Vascular Medicine Research Unit Brigham and Women's Hospital and Harvard Medical School Boston MA USA"},{"name":"Department of Cardiology and Nephrology Mie University School of Medicine Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Li","sequence":"additional","affiliation":[{"name":"Vascular Medicine Research Unit Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kensuke","family":"Noma","sequence":"additional","affiliation":[{"name":"Vascular Medicine Research Unit Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Hiroi","sequence":"additional","affiliation":[{"name":"Vascular Medicine Research Unit Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping\u2010Yen","family":"Liu","sequence":"additional","affiliation":[{"name":"Vascular Medicine Research Unit Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaya","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Nephrology Mie University School of Medicine Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Nephrology Mie University School of Medicine Mie Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James K.","family":"Liao","sequence":"additional","affiliation":[{"name":"Vascular Medicine Research Unit Brigham and Women's Hospital and Harvard Medical School Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,27]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.6.666"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.84.4.458"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI13350"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510444103"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0171r.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.68.1.459"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(97)00317-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nrm1128","article-title":"Rocks: multifunctional kinases in cell behaviour","volume":"4","author":"Riento K.","year":"2003","journal-title":"Nat. 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