Cardiac-specific Overexpression Of Hsp27 Induced Cardiomyopathy Involvement Of Autophagy And Mechanism In The Transgenic Mice

Autophagy is a highly conserved progress, through which damaged or long-lived proteins, macromolecules, or organelles are recycled by using lysosomal degradation machinery. Although the occurrence of autophagy was observed in several cardiac diseases including ischemic or ischemia-reperfusion injury, starvation, pressure overload stress, little is known about the roles of autophagy in the transition of cardiac hypertrophy to heart failure. By using our previously established cardiac hypertrophy model induced by highly expression of Hsp27, we investigated whether autophagy will play an important role in the development of cardiac hypertrophy and heart failure, especially, the transition of cardiac hypertrophy to heart failure. We observed that transgenic mice with high levels of Hsp27 developed cardiomyopathy. The myopathic hearts exhibited an increase in autophagy flux, which was evidenced by increased LC3â…¡/â…  ratio and decreased P62 level measured by Western Blot. Activation of Vps34 was also observed in the hypertrophic hearts. In addition, histological analysis revealed an accumulation of protein aggregation. Our results indicate that over expression of Hsp27 lead to cardiomyopathy, could be due to, at least in part, by Vps34-dependent activation of autophagy.