Alogliptin, a dipeptidyl peptidase-4 inhibitor, regulates the atrial arrhythmogenic substrate in rabbits

Heart Rhythm : the Official Journal of the Heart Rhythm Society
Toshihiko YamamotoToyoaki Murohara

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors were recently reported to have cardioprotective effects via amelioration of ventricular function. However, the role of DPP-4 inhibition in atrial remodeling, especially of the arrhythmogenic substrate, remains unclear. We investigated the effects of a DPP-4 inhibitor, alogliptin, on atrial fibrillation (AF) in a rabbit model of heart failure caused by ventricular tachypacing (VTP). Rabbits subjected to VTP at 380 bpm for 1 or 3 weeks, with or without alogliptin treatment, were assessed using echocardiography, electrophysiology, histology, and immunoblotting and compared with nonpaced animals. VTP rabbits exhibited increased duration of atrial burst pacing-induced AF, whereas administration of alogliptin shortened this duration by 73%. The extent of atrial fibrosis after VTP was reduced by 39% in the alogliptin-treated group. VTP rabbits treated with alogliptin displayed a 1.6-fold increase in left atrial myocardial capillary density compared with nontreated rabbits. A 2-fold increase in endothelial nitric oxide synthase (eNOS) phosphorylation was observed in the left atrium of alogliptin-treated rabbits compared with nontreated rabbits. Moreover, a nitric oxide synthase inhibitor (N(ω)-...Continue Reading

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Citations

Jan 21, 2016·International Journal of Cardiology·Xiaowei ZhangTong Liu
Sep 30, 2015·Cardiovascular Diabetology·Enrique Z Fisman, Alexander Tenenbaum
Apr 28, 2018·Current Opinion in Cardiology·Kalliopi PafiliNikolaos Papanas
Jun 3, 2021·Journal of Clinical Medicine·Paweł Muszyński, Tomasz A Bonda
Jun 12, 2021·Heart Rhythm O2·Hailey J JansenRobert A Rose

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