title: No Additional Effect of DPP-4 Inhibitor on Preventing Atrial Fibrosis in Streptozotocin-Induced Diabetic Rat as Compared With Sulfonylurea.
abstract: 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.
authors.affiliation: Fourth Department of Internal Medicine, Teikyo University School of Medicine University Hospital.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Hayami
authors.forename: Akiko
authors.initials: A
authors.lastname: Sekiguchi
authors.forename: Yu-Ki
authors.initials: YK
authors.lastname: Iwasaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Murakawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001281:Atrial Fibrillation / Q000503:physiopathology / Q000517:prevention & control; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004719:Endomyocardial Fibrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D009570:Nitriles / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013223:Statistics as Topic
chemical_list: C569631:1-((2-adamantyl)amino)acetyl-2-cyano-(S)-pyrrolidine, monohydrochloride; D000893:Anti-Inflammatory Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D000218:Adamantane; D005905:Glyburide