Gene transfer of heat-shock protein 20 protects against ischemia/reperfusion injury in rat hearts.
OBJECTIVE
To explore whether overexpression of HSP20 in the myocardium could protect against ischemia/reperfusion injury in rats.


METHODS
Rat hearts were injected with vector, recombinant adenovirus encoding green fluorescent protein (Ad.GFP) or recombinant adenovirus encoding wild-type HSP20 (Ad.HSP20) in the left ventricle. Four days later, hearts were removed and expression of HSP20 was measured in the left ventricle. Subsets of animals in the vector-, Ad.GFP- , and Ad.HSP20-treated groups were subjected to 20-min ischemia and 120-min reperfusion. Myocardial injury was evaluated by infarct size and level of serum cardiac troponin T and creatine phosphokinase. Apoptosis of cardiomyocytes was determined by TUNEL staining. Cardiac function was evaluated by hemodynamic indexes.


RESULTS
Infarct size and serum cardiac troponin T and creatine phosphokinase levels were significantly reduced in Ad.HSP20-treated hearts compared with vector- and Ad.GFP-treated hearts. The ratio of TUNEL-positive cardiomyocytes to total number of cardiomyocytes in the Ad.HSP20 group was significantly reduced as compared with the vector and Ad.GFP groups. Left ventricular end systolic pressure, and maximal rate of pressure increase (+dp/dt(max)) and decrease (-dp/dt(min)) values were increased significantly, while left ventricular end diastolic pressure was decreased significantly in Ad.HSP20-treated hearts compared with vector- and Ad.GFP-treated hearts.


CONCLUSIONS
These data indicate that the cardioprotective effects of HSP20 may contribute to the reduction of myocardial necrosis and apoptosis in ischemia/reperfusion injury in rats.
Zhu
Yan-hui
YH
Department of Physiology and Pathophysiology, Basic Medical College, Key Laboratory of Molecular Cardiovascular Biology, Ministry of Education, Peking University, Beijing 100083, China.
Ma
Tie-min
TM
Wang
Xian
X
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D003402:Creatine Kinase / Q000097:blood; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D050886:HSP20 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000166:cytology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020107:Troponin T / Q000097:blood
D050886:HSP20 Heat-Shock Proteins; D011994:Recombinant Proteins; D020107:Troponin T; D003402:Creatine Kinase