Lin Shenglan, Wang Yana, Zhang Xiaojin, Kong Qiuyue, Li Chuanfu, Li Yuehua, Ding Zhengnian, Liu Li
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Oxid Med Cell Longev. 2016;2016:2586706. doi: 10.1155/2016/2586706. Epub 2016 Mar 23.
Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation.
衰老诱导的心脏功能障碍是心脏衰老的一个显著特征。热休克蛋白27(HSP27)可保护心脏功能免受缺血或化学刺激的影响。我们推测HSP27可减轻心脏衰老。实验采用心脏特异性表达HSP27基因的转基因(Tg)小鼠和野生型(WT)同窝小鼠。超声心动图显示,与年轻WT小鼠相比,老年WT小鼠的心脏功能显著下降。与之形成鲜明对比的是,与老年WT小鼠相比,老年Tg小鼠中衰老诱导的心脏功能损害有所减轻。老年Tg小鼠心脏中心脏衰老标志物的水平低于老年WT小鼠心脏。与老年WT心脏相比,在老年Tg心脏中检测到的间质纤维化更少,活性氧和泛素结合蛋白的含量更低。此外,老年Tg心脏中LC3-II和p62的积累低于老年WT心脏。老年Tg心脏中Atg13、Vps34和Rab7的水平也高于老年WT心脏。此外,老年Tg心脏中PINK1和Parkin的水平高于老年WT心脏,这表明老年Tg心脏中的线粒体自噬被激活。综上所述,HSP27减轻了心脏衰老,这一作用涉及抗氧化和线粒体自噬激活。