Decreased RhoA expression in myocardium of diabetic rats

Diabetic cardiomyopathy is one of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague-Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 ± 7 beats/min in diabetic rats. There was a 62% decrease (p < 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 ± 6.7 × 10⁶ molecules/μg total RNA) compared with controls (101 ± 10.3 × 10⁶ molecules/μg total RNA). Western blot showed a 33% decrease in total RhoA protein expression in heart tissues of diabetic rats compared with controls (p < 0.05). A reduced RhoA translocation in heart tissues of diabetic rats was determined by a 64% decrease in membrane-bound RhoA (p < 0.01 vs. control group), indicating that the activation of RhoA is markedly reduced in diabetic myocardium. Our data suggest that down-regulated RhoA may be involved in cardiomyopathy in diabetic rats.