[Overexpression of heat shock protein 27 reduces mortality and attenuates cardiac dysfunction induced by doxorubicin in a transgenic mouse model].
OBJECTIVE
To observe the effects of heat shock protein 27 (Hsp27) overexpression on doxorubicin (Dox) induced mortality and cardiac dysfunction in a transgenic (TG) mouse model.


METHODS
A linear DNA constituted of alpha-myosin heavy chain (alpha-MHC) promoter, human Hsp27cDNA and poly A was microinjected into fertilized eggs to generate transgenic mice and mice containing the transgene were identified by polymerase chain reaction and independent transgenic lines were established. Following successful transmission, tissues including heart, lung, liver, brain, skeleton muscle, spleen and kidney were screened by Western blot to confirm the cardiac specific expression of the transgene. TG and wild type littermates (WT) received a single dosage of Dox injection (25 mg/kg IP) or saline injection and observed for 5 days. Mice mortality was noticed and left ventricular (LV) hemodynamics were measured at day 5 in surviving mice. Cardiomyocyte apoptosis was evaluated by TUNEL assay at day 3 post Dox or saline injections in a separate group.


RESULTS
Three independent transgenic lines were generated, and all of them expressed cardiac specific Hsp27. Five days mortality was significantly reduced in TG group than that in WT group post Dox (P < 0.01), Dox induced cardiac dysfunction and cardiomyocyte apoptosis were also significantly attenuated in TG mice compared to WT mice (P < 0.05).


CONCLUSIONS
Overexpression of Hsp27 reduced mortality, attenuated left ventricular dysfunction and cardiomyocyte apoptosis induced by Dox in a transgenic mouse model.
Liu
Li
L
Department of Geriatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Zhang
Xiao-jin
XJ
Qian
Bo
B
Min
Xiao-yan
XY
Cheng
Yun-lin
YL
D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D004317:Doxorubicin; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D006360:Heat-Shock Proteins; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D032383:Myocytes, Cardiac / Q000166:cytology; D018384:Oxidative Stress; D018487:Ventricular Dysfunction, Left / Q000378:metabolism
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D004317:Doxorubicin