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

International Journal of Molecular Sciences

Huang Ying¹  Mao-Chun Xu³  Jing-Hua Tan¹  Jing-Hua Shen¹  Hao Wang²  Dai-Fu Zhang¹ 

[1]Department of Cardiology, Shanghai Pu Dong New Area People’s Hospital, Shanghai 200120, China

[2] E-Mails:

[3]Fudan University Shanghai Medical College Centre of Medical Experiments, Shanghai 200040, China

[4]Department of Cardiology, Huashan Hospital of Fudan University, Shanghai 200040, China

[5] E-Mail:

关键词: pressure overload;    cardiac hypertrophy;    HDAC2;    Jak2;    Ang-II;   

DOI  :  10.3390/ijms151120240

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.