Cardiac remodeling rather than disturbed myocardial energy metabolism is associated with cardiac dysfunction in diabetic rats

Abstract

Diabetes mellitus (DM) alters the energy substrate metabolism in the heart and the early sign of diabetic cardiomyopathy is the diastolic dysfunction. Although it is known that the extracellular matrix must be altered in the presence of diabetes, its local regulation has not been fully elucidated. Our aim was to evaluate in vivo left ventricular (LV) structure; function and bioenergetics in streptozotocin (STZ) induced diabetes mellitus. Cardiac function was evaluated using echocardiography in anesthetized Sprague–Dawley rats 12 weeks after injection of STZ and in age-matched control rats before and after atrial pacing. In vivo ³¹P magnetic resonance spectroscopy was done to measure the phosphocreatine (PCr) to ATP ratio. Myocardial protein expression of metalloproteinases MMP-2, -9, tissue inhibitor TIMP-1, -2 and collagen was measured using Western blot. Bodyweight (BW) was decreased in diabetic rats. Heart weight/BW and LV mass/BW ratios were higher in diabetic animals compared to controls (2.3 ± 08 vs 2.1 ± 08 mg/g p <0.05). Heart rate was lower in diabetic rats (293 ± 20 vs 394 ± 36 bpm p <0.05). The velocity of circumferential shortening and peak aortic velocity were lower in diabetic animals and were more pronounced during atrial pacing. The basal PCr/ATP ratio was not different in the two groups. Total collagen was higher in diabetic rats (3.8 ± 0.3 vs 2.9 ± 01 mg/g, p <0.05). Protein expression of MMP-2 was significantly diminished in diabetic rats by ≈ 60%, while MMP-9, TIMP-1 and -2 were unchanged. Streptozotocin induced diabetes led to increased LV/bodyweight, increased collagen content, and diminished MMP-2 with no change in PCr/ATP. Therefore, remodeling rather than disturbed energetics may underlie diabetic cardiomyopathy.