No Additional Effect of DPP-4 Inhibitor on Preventing Atrial Fibrosis in Streptozotocin-Induced Diabetic Rat as Compared With Sulfonylurea

Chronic inflammation is known to occur in diabetes mellitus (DM) and contributes to atrial fibrosis, possible substrates for atrial fibrillation. We tested the hypothesis that dipeptidyl peptidase (DPP)-4 inhibitors prevent the formation of atrial fibrosis through their anti-inflammatory activity, beyond the effects of controlling blood glucose.DM models obtained by administration of streptozotocin (STZ) were divided into 3 groups: with PKF275-055, a DPP-4 inhibitor in group D, glibenclamide in group SU, and no additional drug in group P. At 8 weeks after STZ administration, the heart was subjected to Masson trichrome staining and immunohistochemistry with anti-ED2, ED3, and smooth muscle actin antibody.The % area of fibrosis in atria of group P accounted for 14.7% ± 4.1%, showing a significant increase in fibrosis when compared with the control group. In group SU, the % area accounted for 7.9% ± 2.9%, indicating significant deceased fibrosis by sulfonylurea. Meanwhile, we could not find significant differences in group D when compared to group P or group SU. While ED3-positive cells increased in group P (1.12% ± 0.24%), they were significantly decreased in groups D and SU (0.41% ± 0.22% and 0.55% ± 0.29%, respectively). Between group D and SU, however, there were no significant differences in the amount of cells positive to ED2, ED3, and smooth muscle actin antibodies.In STZ-induced DM rats, administration of sulfonylurea and DPP-4 inhibitors inhibited inflammation and fibrosis of the atria. However, no significant differences were observed between the 2 antidiabetic drugs.