Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
J Cell Biochem. 2011 Jul;112(7):1787-94. doi: 10.1002/jcb.23091.
Cardiac hypertrophy, a major determinant of heart failure, is associated with heat shock proteins (HSPs). HSP75 has been reported to protect against environmental stresses; however, its roles in cardiac hypertrophy remain unclear. Here, we generated cardiac-specific inducible HSP75 transgenic mice (TG) and cardiac hypertrophy was developed at 4 weeks after aortic banding in TG mice and wild-type littermates. The results revealed that overexpression of HSP75 prevented cardiac hypertrophy and fibrosis as assessed by heart weight/body weight ratio, heart weight/tibia length ratio, echocardiographic and hemodynamic parameters, cardiomyocyte width, left ventricular collagen volume, and gene expression of hypertrophic markers. Further studies showed that overexpression of HSP75 inhibited the activation of TAK/P38, JNK, and AKT signaling pathways. Thus, HSP75 likely reduces the hypertrophy and fibrosis induced by pressure overload through blocking TAK/P38, JNK, and AKT signaling pathways.
心肌肥厚是心力衰竭的主要决定因素，与热休克蛋白（HSPs）有关。已经有报道称 HSP75 可抵抗环境压力；然而，其在心肌肥厚中的作用仍不清楚。在这里，我们生成了心脏特异性诱导 HSP75 转基因小鼠（TG），并在 TG 小鼠和野生型同窝仔鼠主动脉缩窄 4 周后发展出心肌肥厚。结果表明，HSP75 的过表达可预防心脏重量/体重比、心脏重量/胫骨长度比、超声心动图和血流动力学参数、心肌细胞宽度、左心室胶原容积以及肥厚标志物基因表达评估的心肌肥厚和纤维化。进一步的研究表明，HSP75 的过表达抑制了 TAK/P38、JNK 和 AKT 信号通路的激活。因此，HSP75 可能通过阻断 TAK/P38、JNK 和 AKT 信号通路来减少压力超负荷引起的心肌肥厚和纤维化。
