Over-expression of heat shock protein 27 attenuates doxorubicin-induced cardiac dysfunction in mice.
BACKGROUND
Oxidative stress and myocyte apoptosis are thought to play an important role in the pathogenesis, progression and prognosis of heart failure (HF). Heat shock protein 27 (Hsp27) has been found to confer resistance to oxidative stress in cultured cells; however, the role of Hsp27 in in-vivo hearts remains to be determined.


OBJECTIVE
To investigate the effects of Hsp27 over-expression on doxorubicin-induced HF.


RESULTS
Transgenic mice (TG) with cardiac specific over-expression of Hsp27 and their wild type littermates (WT) were challenged with doxorubicin (25 mg/kg, IP) to induce HF. At day 5, TG mice had significantly improved cardiac function and viability and decreased loss of heart weight following doxorubicin exposure compared with WT. In another parallel experiment, doxorubicin-induced increased levels of reactive oxygen species, protein carbonylation, apoptosis and morphologic changes were detected in the mitochondria in WT hearts, whereas these effects were markedly attenuated in TG hearts. In addition, upregulation of heat shock protein 70 and heme oxygenase-1 was present in the TG hearts after doxorubicin stimulation in comparison to WT hearts.


CONCLUSIONS
These findings indicate that Hsp27 may play a key role in resistance to doxorubicin-induced cardiac dysfunction.
Liu
Li
L
Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
Zhang
Xiaojin
X
Qian
Bo
B
Min
Xiaoyan
X
Gao
Xiang
X
Li
Chuanfu
C
Cheng
Yunlin
Y
Huang
Jun
J
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects; D055551:HSP27 Heat-Shock Proteins; D006333:Heart Failure / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000032:analysis
D000903:Antibiotics, Antineoplastic; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486699:Hspb2 protein, mouse; D017382:Reactive Oxygen Species; D004317:Doxorubicin