Phosphorylated heat shock protein 27 is involved in enhanced heart tolerance to ischemia in short-term type 1 diabetic rats.
OBJECTIVE
To examine the tolerance of type 1 diabetic hearts to ischemia and reperfusion injury. Myocardial contents of 27-kDa and 70-kDa heat shock proteins (hsp) as well as phosphorylated hsp27 were also determined.


METHODS
Hearts from hyperglycemic rats 3 weeks after streptozocin injection and age-matched normal rats were subjected to ischemia and reperfusion in vitro. Cardiac function and electrocardiogram were recorded throughout experiments. Myocardial heat shock proteins were detected with Western blot.


RESULTS
Despite depressed systolic function at the baseline, diabetic hearts exhibited considerable enhancement in post-ischemic heart function, manifested by an increase in the maximal rate of left ventricular pressure rise and fall (post-ischemic dp/dtmax and dp/dtmin were 560+/-117 and -313+/-68 mmHg/s in control, n=7, 1249+/-57 and -1204+/-36 mmHg/s in diabetes, n=10, P<0.01). Reperfusion ventricular fibrillation in the diabetic group were attenuated compared with controls (1.5+/-0.3 vs 7.2+/-2.1 min in control, P<0.01). The increased heart resistance to ischemia in diabetes was associated with hyperglycemia and accompanied by enhanced expression of myocardial phosphorylated hsp27 with normal aortic vessel relaxation. Cardioprotection was abrogated by metabolic correction with insulin and accompanied by phospho-hsp27 reduction.


CONCLUSIONS
Heart resistance to ischemia is increased in type 1 diabetes, and hyperglycemia may present a mild yet stressful stimulus leading to upregulation of endogenous stress protein, which may play a potential role in cardioprotection and compensate for detrimental effects of hyperglycemia in diabetes.
Chen
Hong
H
Department of Pharmacology, Shanghai Second Medical University, Shanghai 200025, China. hchen100@hotmail.com
Wu
Xing-Jun
XJ
Lu
Xi-Yuan
XY
Zhu
Liang
L
Wang
Li-Ping
LP
Yang
Huang-Tian
HT
Chen
Hong-Zhuan
HZ
Yuan
Wen-Jun
WJ
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D017725:Ventricular Pressure / Q000187:drug effects
D001786:Blood Glucose; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007328:Insulin; D013311:Streptozocin