HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation.
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.
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Shenglan
S
Lin
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Yana
Y
Wang
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Xiaojin
X
Zhang
Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Qiuyue
Q
Kong
Department of Surgery, East Tennessee State University, Johnson City, TN 37614, USA.
Chuanfu
C
Li
Department of Pathophysiology, Nanjing Medical University, Nanjing 210029, China.
Yuehua
Y
Li
Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Zhengnian
Z
Ding
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, China.
Li
0000-0002-8054-562X
L
Liu
D000375:Aging; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D000071193:Autophagy-Related Protein 7 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D004452:Echocardiography; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D063306:Mitophagy / Q000502:physiology*; D018832:Molecular Chaperones; D009206:Myocardium / Q000378:metabolism*; D050050:Protein Carbonylation; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000099202:PTEN-Induced Putative Kinase
D000975:Antioxidants; D000071193:Autophagy-Related Protein 7; D019941:Cyclin-Dependent Kinase Inhibitor p16; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D011494:Protein Kinases; D017382:Reactive Oxygen Species; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; D000099202:PTEN-Induced Putative Kinase; C502661:Atg7 protein, mouse; C057725:HSPB1 protein, human; C480860:Map1lc3b protein, mouse; C000716463:rab7 GTP-binding proteins, human; C000716465:rab7 GTP-binding proteins, mouse; C111567:parkin protein