Phosphorylated heat shock protein 27 is involved in enhanced heart tolerance to ischemia in short-term type 1 diabetic rats
Abstract
Aim: 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 postischemic 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 560plusminus117 and -313plusminus68 mmHg/s in control, n=7, 1249plusminus57 and -1204plusminus36 mmHg/s in diabetes, n=10, P < 0.01). Reperfusion ventricular fibrillation in the diabetic group were attenuated compared with controls (1.5plusminus0.3 vs 7.2plusminus2.1 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.
Conclusion: 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.
Keywords:
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 postischemic 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 560plusminus117 and -313plusminus68 mmHg/s in control, n=7, 1249plusminus57 and -1204plusminus36 mmHg/s in diabetes, n=10, P < 0.01). Reperfusion ventricular fibrillation in the diabetic group were attenuated compared with controls (1.5plusminus0.3 vs 7.2plusminus2.1 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.
Conclusion: 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.