{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T08:19:32Z","timestamp":1789373972534,"version":"build-2803163510"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2014,11,5]],"date-time":"2014-11-05T00:00:00Z","timestamp":1415145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pressure overload induces cardiac hypertrophy through activation of Janus kinase 2 (Jak2), however, the underlying mechanisms remain largely unknown. In the current study, we tested whether histone deacetylase 2 (HDAC2) was involved in the process.  We found that angiotensin II (Ang-II)-induced re-expression of fetal genes (Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)) in cultured cardiomyocytes was prevented by the Jak2 inhibitor AG-490 and HDAC2 inhibitor Trichostatin-A (TSA), or by Jak2\/HDAC2 siRNA knockdown. On the other hand, myocardial cells with Jak2  or HDAC2 over-expression were hyper-sensitive to Ang-II. In vivo, pressure overload  by transverse aorta binding (AB) induced a significant cardiac hypertrophic response  as well as re-expression of ANP and BNP in mice heart, which were markedly reduced  by AG-490 and TSA. Significantly, AG-490, the Jak2 inhibitor, largely suppressed pressure overload-\/Ang-II-induced HDAC2 nuclear exportation in vivo and in vitro. Meanwhile, TSA or HDAC2 siRNA knockdown reduced Ang-II-induced ANP\/BNP expression in Jak2 over-expressed H9c2 cardiomyocytes. Together, these results suggest that HDAC2 might be a downstream effector of Jak2 to mediate cardiac hypertrophic response by pressure overload or Ang-II.<\/jats:p>","DOI":"10.3390\/ijms151120240","type":"journal-article","created":{"date-parts":[[2014,11,6]],"date-time":"2014-11-06T02:48:56Z","timestamp":1415242136000},"page":"20240-20253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pressure Overload-Induced Cardiac Hypertrophy Response Requires Janus Kinase 2-Histone Deacetylase 2 Signaling"],"prefix":"10.3390","volume":"15","author":[{"given":"Huang","family":"Ying","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Pu Dong New Area People's Hospital, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Chun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Huashan Hospital of Fudan University, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Hua","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Pu Dong New Area People's Hospital, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Hua","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Pu Dong New Area People's Hospital, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wang","sequence":"additional","affiliation":[{"name":"Fudan University Shanghai Medical College Centre of Medical Experiments, Shanghai 200040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai-Fu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Pu Dong New Area People's Hospital, Shanghai 200120, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2014,11,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1146\/annurev.physiol.63.1.391","article-title":"Cytoplasmic signaling pathways that regulate cardiac hypertrophy","volume":"63","author":"Molkentin","year":"2001","journal-title":"Annu. 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