Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy.
Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy.
复制标题
通过RNA干扰沉默肌营养蛋白基因可导致心脏肥大消退。
DOI：
10.1152/ajpheart.00294.2009
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Sen,Subha
中科院分区：
文献类型：
--
作者：
Gupta,Sudhiranjan;Maitra,Ratan;Young,Dave;Gupta,Anasuya;Sen,Subha
Myotrophin-induced activation of NF-κB has been shown to be associated with cardiac hypertrophy (CH) that progresses to heart failure (HF). In the present study, we examined the cause-and-effect relationship between myotrophin and NF-κB activation using small hairpin RNA (shRNA) against myotrophin both in vitro (using neonatal rat myocytes) and in vivo [using myotrophin transgenic (Myo-Tg) mice, which overexpress myotrophin in the heart, develop CH, and gradually progress to HF]. Among several lentiviral vectors expressing myotrophin shRNAs, L-sh-109 showed the best silencing effect at both the mRNA (155.3 ± 5.9 vs. 32.5 ± 5.5,P< 0.001) and protein levels associated with a significant reduction of atrial natriuretic factor (ANF) and NF-κB. In vivo, when L-sh-109 was delivered directly into the hearts of 10-wk-old Myo-Tg mice, we observed a significant regression of cardiac mass (8.0 vs. 5.7 mg/g,P< 0.001) and myotrophin gene expression (54.5% over untreated Myo-Tg mice,P< 0.001) associated with a reduction in ANF and NF-κB signaling components. Our data suggest that using RNA interference to silence the myotrophin gene prevents NF-κB activation, associated with an attenuation of CH. This strategy could be an excellent therapeutic means for the treatment of CH and HF.
