NF-κB activation is required for the development of cardiac hypertrophy in vivo
NF-κB activation is required for the development of cardiac hypertrophy in vivo
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DOI：
10.1152/ajpheart.00124.2004
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Li, CF
中科院分区：
文献类型：
--
作者：
Li, YH;Ha, TZ;Li, CF
在本研究中，我们研究了NF-kappaB激活是否需要体内心脏肥厚。主动脉束带诱导大鼠心肌肥厚1、3、5天和1 ~ 6周，以年龄匹配的假手术大鼠为对照。在另一组大鼠中，将ikappab - α显性阴性突变体（ikappab - α - ham） （NF-kappaB激活的超抑制因子）或吡咯烷二硫代氨基甲酸酯（PDTC）（一种可以抑制NF-kappaB激活的抗氧化剂）给予主动脉带大鼠3周。与年龄匹配的假对照组相比，心脏重量与体重比在主动脉封带后第5天显著增加，在第4周达到峰值，并在第6周保持升高。心房钠肽和脑钠肽mRNA的表达在主动脉封带1周后显著升高，在2 - 3周达到最大值，在6周时与年龄匹配的假对照组相比仍保持升高。与年龄匹配的假对照组相比，NF-kappaB活性在第1天显著升高，在第3周达到峰值，并在第6周保持升高，ikk - β活性在第1天显著升高，在第5天达到峰值，然后下降，但在第6周保持升高。通过心脏转染IkappaB-alphaM或通过PDTC治疗抑制体内NF-kappaB的激活，可显著减轻体内心肌肥厚的发展，同时NF-kappaB活性降低。我们的研究结果表明，NF-kappaB激活是体内心肌肥厚发展所必需的，NF-kappaB可能是体内抑制心肌肥厚发展的重要靶点。
In the present study, we examined whether NF-kappaB activation is required for cardiac hypertrophy in vivo. Cardiac hypertrophy in rats was induced by aortic banding for 1, 3, and 5 days and 1 - 6 wk, and age-matched sham-operated rats served as controls. In a separate group of rats, an IkappaB-alpha dominant negative mutant (IkappaB-alphaM), a superrepressor of NF-kappaB activation, or pyrrolidinedithiocarbamate (PDTC), an antioxidant that can inhibit NF-kappaB activation, was administered to aortic-banded rats for 3 wk. The heart weight-to-body weight ratio was significantly increased at 5 days after aortic banding, peaked at 4 wk, and remained elevated at 6 wk compared with age-matched sham controls. Atrial natriuretic peptide and brain natriuretic peptide mRNA expressions were significantly increased after 1 wk of aortic banding, reached a maximum between 2 and 3 wk, and remained increased at 6 wk compared with age-matched sham controls. NF-kappaB activity was significantly increased at 1 day, reached a peak at 3 wk, and remained elevated at 6 wk, and IKK-beta activity was significantly increased at 1 day, peaked at 5 days, and then decreased but remained elevated at 6 wk after aortic banding compared with age-matched sham controls. Inhibiting NF-kappaB activation in vivo by cardiac transfection of IkappaB-alphaM or by PDTC treatment significantly attenuated the development of cardiac hypertrophy in vivo with a concomitant decrease in NF-kappaB activity. Our results suggest that NF-kappaB activation is required for the development of cardiac hypertrophy in vivo and that NF-kappaB could be an important target for inhibiting the development of cardiac hypertrophy in vivo.