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Pressure overload-induced cardiac hypertrophy response requires janus kinase 2-histone deacetylase 2 signaling.

International journal of molecular sciences (2014-11-08)
Huang Ying, Mao-Chun Xu, Jing-Hua Tan, Jing-Hua Shen, Hao Wang, Dai-Fu Zhang
ABSTRACT

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.

MATERIALS
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