A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy
A cell-permeable NFAT inhibitor peptide prevents pressure-overload cardiac hypertrophy
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DOI：
10.1111/j.1747-0285.2006.00360.x
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发表时间：
2006-03-01
影响因子：
3
通讯作者：
Matsui, H
中科院分区：
文献类型：
--
作者：
Kuriyama, M;Matsushita, M;Matsui, H
在压力超负荷心脏肥大的发展过程中，激活T细胞级联的钙调神经磷酸酶-核因子的激活先前已在许多研究中报道过。此外，涉及钙调神经磷酸酶抑制剂（例如 FK506 和环孢菌素 A）的大量药理学研究现已证明，这些药物可以预防心脏的此类肥大反应。然而，人们对钙调神经磷酸酶下游效应器（活化 T 细胞的核因子）的作用知之甚少。我们目前的研究通过采用最近开发的细胞渗透性活化 T 细胞核因子抑制肽，进一步研究了活化 T 细胞核因子在压力超负荷心脏肥大中的作用。大鼠心脏因 4 周的主动脉结扎而承受压力超负荷，然后用这种活化 T 细胞抑制肽的细胞渗透性核因子和对照肽进行处理。研究发现，用抑制剂治疗可显着降低心脏重量/体重比、心肌细胞大小以及血清脑钠尿肽和心房钠尿肽水平。这些结果表明，活化 T 细胞的核因子在压力超负荷期间心脏肥大的发展中发挥关键作用。通过特定的抑制肽抑制活化 T 细胞的核因子是表征心脏肥大分子机制以及寻找新的有希望的疾病疗法的合适方法。
The activation of the calcineurin-nuclear factor of activated T cells cascade during the development of pressure-overload cardiac hypertrophy has been previously reported in a number of studies. In addition, numerous pharmacological studies involving calcineurin inhibitors such as FK506 and cyclosporine A have now demonstrated that these agents can prevent such hypertrophic responses in the heart. However, little is known regarding the roles of the calcineurin downstream effecter - nuclear factor of activated T cells. Our present study has further examined the roles of nuclear factor of activated T cells in pressure-overload cardiac hypertrophy by employing a recently developed cell-permeable nuclear factor of activated T cells inhibitor peptide. Rat hearts were subjected to pressure overload attributable by 4 weeks of aortic banding, and then treated with this cell-permeable nuclear factor of activated T cells inhibitor peptide and a control peptide. Treatment with the inhibitor was found to significantly decrease the heart weight/body weight ratio, the size of cardiac myocytes, and the serum brain natriuretic peptide and atrial natriuretic peptide levels. These results suggest that nuclear factor of activated T cells functions in a key role in the development of cardiac hypertrophy during pressure overload. Inhibition of nuclear factor of activated T cells by a specific inhibitor peptide is a suitable method for characterization of the molecular mechanisms underlying cardiac hypertrophy as well as in the search for new promising therapies for disease.