© 2007 European Society of Cardiology
Over-expression of heat shock protein 27 attenuates doxorubicin-induced cardiac dysfunction in mice
a Department of Geriatrics, First Affiliated Hospital with Nanjing Medical University Nanjing, China
b National Resource Center of Mutant mice, Nanjing University Nanjing, China
c Department of Surgery, East Tennessee State University, Johnson City TN, USA
d Department of Cardiology, First Affiliated Hospital with Nanjing Medical University Guang Zhou Rd 300, Nanjing 210029, China
* Corresponding author. Tel.: +86 25 83718836 6315; fax: +86 25 83724440. E-mail address: huangjun{at}njmu.edu.cn
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Abstract |
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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.
Aim: To investigate the effects of Hsp27 over-expression on doxorubicin-induced HF.
Methods and 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.
Conclusion: These findings indicate that Hsp27 may play a key role in resistance to doxorubicin-induced cardiac dysfunction.
Key Words: Heart failure • Small heat shock protein • Free radical • Apoptosis • Doxorubicin • Haemodynamics
Received June 30, 2006; Revised January 19, 2007; Accepted March 21, 2007
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