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Int. J. Mol. Sci. 2014, 15(11), 20240-20253;

Pressure Overload-Induced Cardiac Hypertrophy Response Requires Janus Kinase 2-Histone Deacetylase 2 Signaling

Department of Cardiology, Shanghai Pu Dong New Area People's Hospital, Shanghai 200120, China
Department of Cardiology, Huashan Hospital of Fudan University, Shanghai 200040, China
Fudan University Shanghai Medical College Centre of Medical Experiments, Shanghai 200040, China
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 10 July 2014 / Revised: 23 September 2014 / Accepted: 9 October 2014 / Published: 5 November 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: pressure overload; cardiac hypertrophy; HDAC2; Jak2; Ang-II pressure overload; cardiac hypertrophy; HDAC2; Jak2; Ang-II

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Ying, H.; Xu, M.-C.; Tan, J.-H.; Shen, J.-H.; Wang, H.; Zhang, D.-F. Pressure Overload-Induced Cardiac Hypertrophy Response Requires Janus Kinase 2-Histone Deacetylase 2 Signaling. Int. J. Mol. Sci. 2014, 15, 20240-20253.

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