Effects of pravastatin on diabetic cardiomyopathy according to the blood glucose control in type 1 diabetic rats

Abstract

Background: Although statins have been suggested to attenuate the progression of diabetic cardiomyopathy, it remains unclear whether statins are protective in diabetic hearts when blood glucose is not controlled. We evaluated the effect of pravastatin on diabetic rat hearts according to the presence of glycemic control.<br/> Methods: Seven-week-old male Lewis rats (n = 87) were randomly divided into five groups: control (group C), diabetes (D), diabetes with insulin (I), diabetes with pravastatin (P), and diabetes with insulin and pravastatin (IP). Diabetes was induced using a single intravenous injection of streptozotocin (65 mg/kg). After diagnosing diabetes (blood glucose > 300 mg/dl), insulin (2-10 U/kg, twice a day) and/or pravastatin (20-25 mg/kg/day) were administered depending on the group assignment. Eight weeks after diabetic induction, the heart was extracted following echocardiography. Cardiac fibrosis was analyzed using Massons trichrome stain. Cardiac expression of collagen I/III, matrix metalloproteinase (MMP)-2, MMP-9, and angiotensin converting enzyme (ACE)/ACE2 were evaluated by immunohistochemistry and/or Western blot. Enzyme-linked immunosorbent assay was used for measuring reactive oxygen species (ROS). <br/> Results: Diabetic groups without glycemic control (groups D and P) showed significantly impaired diastolic function and significantly increased levels of cardiac fibrosis, collagen I/III, MMP-2, and MMP-9. ROS production was also significantly increased in groups D and P. However, there were no significant differences in most outcomes among the control and two glucose-controlled diabetic groups (groups I and IP). Cardiac ACE2 expression was more preserved, while ACE expression was lower in groups C and IP than in the other groups (D, I, and P).<br/> Conclusion: Our study suggests that glycemic control using insulin rather than pravastatin attenuates the progression of diabetic cardiomyopathy. However, further study is required to evaluate the usefulness of statins in protecting diabetic hearts. <br/>