Phosphorylated heat shock protein 27 is involved in enhanced heart tolerance to ischemia in short-term type 1 diabetic rats

Aim:To examine the tolerance of type 1 diabetic hearts to ischemia and reperfusioninjury.Myocardial contents of 27-kDa and 70-kDa heat shock proteins(hsp)aswell as phosphorylated hsp27 were also determined.Methods:Hearts from hyper-glycemic rats 3 weeks after streptozocin injection and age-matched normal ratswere subjected to ischemia and reperfusion in vitro.Cardiac function and electro-cardiogram were recorded throughout experiments.Myocardial heat shock pro-teins were detected with Western blot.Results:Despite depressed systolic func-tion at the baseline,diabetic hearts exhibited considerable enhancement in post-ischemic heart function,manifested by an increase in the maximal rate of leftventricular pressure rise and fall(post-ischemic dp/dtmaxand dp/dtminwere 560±117and-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 at-tenuated compared with controls(1.5±0.3 vs 7.2±2.1 min in control,P<0.01).Theincreased heart resistance to ischemia in diabetes was associated with hypergly-cemia and accompanied by enhanced expression of myocardial phosphorylatedhsp27 with normal aortic vessel relaxation.Cardioprotection was abrogated bymetabolic correction with insulin and accompanied by phospho-hsp27 reduction.Conclusion:Heart resistance to ischemia is increased in type 1 diabetes,andhyperglycemia may present a mild yet stressful stimulus leading to upregulationof endogenous stress protein,which may play a potential role in cardioprotectionand compensate for detrimental effects of hyperglycemia in diabetes.