1. The dipeptidyl peptidase-4 inhibitor-sitagliptin modulates calcium dysregulation, inflammation, and PPARs in hypertensive cardiomyocytes.
- Author
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Lee, T-I, Kao, Y-H, Chen, Y-C, Huang, J-H, Hsu, M-I, and Chen, Y-J
- Subjects
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CD26 antigen , *SITAGLIPTIN , *ENZYME inhibitors , *CALCIUM deficiency , *INFLAMMATION , *HEART cells , *PEROXISOME proliferator-activated receptors , *WESTERN immunoblotting - Abstract
Abstract: Background: Hypertension induces cardiac dysfunction, calcium (Ca2+) dysregulation, and arrhythmogenesis. Dipeptidyl peptidase (DPP)-4 inhibitors, an antidiabetic agent with anti-inflammation and anti-hypertension potential, may regulate peroxisome proliferator-activated receptors (PPARs)-α, -γ, and -δ and Ca2+ homeostasis. Objective: The purpose of this study was to investigate whether DPP-4 inhibitor, sitagliptin, can modulate PPARs and Ca2+ handling proteins in hypertensive hearts. Methods: A Western blot analysis was used to evaluate protein expressions of myocardial PPAR isoforms, tumor necrosis factor (TNF)-α, interleukin (IL)-6, sarcoplasmic reticulum ATPase (SERCA2a), Na+–Ca2+ exchanger (NCX), ryanodine receptor (RyR), voltage-dependent Ca2+ (CaV1.2), slow-voltage potassium currents (Kvs), angiotensin II type 1 receptor (AT1R), and receptor of advanced glycated end-products (RAGE) from Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with sitagliptin (10mg/kg for 4weeks). Conventional microelectrodes were used to record action potentials (APs) in the ventricular myocytes from each group. Results: Compared to the control group, SHR had lower cardiac PPAR-α and PPAR-δ protein expressions, but had greater cardiac PPAR-γ levels, and TNF-α, IL-6, RAGE, and AT1R protein expressions, which were ameliorated in the sitagliptin-treated SHR. SHR had prolonged QT interval and AP duration with less SERCA2a and RyR, and greater CaV1.2 expressions, which were also attenuated in sitagliptin-treated SHR. Conclusions: Sitagliptin significantly changed the cardiac electrophysiological characteristics and Ca2+ regulation, which may have been caused by its effects on cardiac PPARs, proinflammatory cytokines, and AT1R. [Copyright &y& Elsevier]
- Published
- 2013
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