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Over‐expression of heat shock protein 27 attenuates doxorubicin‐induced cardiac dysfunction in mice
Author(s) -
Liu Li,
Zhang Xiaojin,
Qian Bo,
Min Xiaoyan,
Gao Xiang,
Li Chuanfu,
Cheng Yunlin,
Huang Jun
Publication year - 2007
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1016/j.ejheart.2007.03.007
Subject(s) - hsp27 , doxorubicin , heat shock protein , medicine , heart failure , oxidative stress , downregulation and upregulation , hsp70 , reactive oxygen species , apoptosis , endocrinology , heme oxygenase , cardiac function curve , glutathione , shock (circulatory) , microbiology and biotechnology , biology , chemotherapy , biochemistry , heme , enzyme , gene
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.