[Heat shock protein 27 attenuated doxorubicin-induced myocardial damage by reducing cardiomyocyte apoptosis, mitochondria damage and protein carbonylation].
OBJECTIVE
Oxidative stress and apoptosis play a critical role in the pathogenesis of congestive heart failure (CHF) induced by doxorubicin (Dox) or ischemia/reperfusion. Heat shock protein 27 (Hsp27) could reduce oxidative stress induced apoptosis in various cell types in vitro and attenuate ischemia/reperfusion induced cardiac dysfunction in isolated perfused mouse heart. In this study, we investigated the impact of Hsp27 overexpression on oxidative stress and apoptosis in Dox-induced mice cardiac dysfunction model.


METHODS
Both Hsp27 transgenic mice (TG) and wild type littermates (WT) received a single dosage of Dox (25 mg/kg IP) or saline. On day 3, histological examinations (Paraffin section and HE staining, mitochondria ultrastructure), in situ cardiomyocytes apoptosis assay (TUNEL, immunohistochemistry against alpha-actinin for cardiomyocytes, hoechst33342 for nuclei staining), protein oxidative damage assay (immunoblot against DNP) were performed on cardiac tissue samples. Pleural effusion and histological changes of heart and lung were examined in dead mice.


RESULTS
(1) Significant pleural effusion, pulmonary congestion, alveoli collapse and extravasated red blood cells were observed in all died mice. (2) Pronounced cardiomyocyte damages and inhomogeneous HE staining were observed in almost all dead mice except for one TG mouse died at day 4 which showed homogeneous HE staining and only slightly cardiomyocyte damages. (3) Cardiac fibrosis was presented in WT mice but not in TG mice. (4) Dox-induced cardiomyocyte apoptosis and protein carbonylation were significantly attenuated in TG mice compared those in WT mice. (5) Severity of Dox-induced mitochondria damage including increased density, swollen cristae and loss of cristae definition was significantly reduced in TG mice compared to that in WT mice were seen in all the examined myocytes of the LV myocardium samples of Dox-treated mice.


CONCLUSIONS
Hsp27 could attenuate Dox-induced myocardial damage by reducing cardiomyocyte apoptosis, mitochondria damage and protein carbonylation.
Liu
Li
L
Department of Geriatrics, First Affiliated Hospital with 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; D004317:Doxorubicin; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics*; D006333:Heart Failure / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D018384:Oxidative Stress; D050050:Protein Carbonylation
D055551:HSP27 Heat-Shock Proteins; D004317:Doxorubicin