The dipeptidyl peptidase-4 inhibitor-sitagliptin modulates calcium dysregulation, inflammation, and PPARs in hypertensive cardiomyocytes

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27 引文 斯高帕斯(Scopus)

摘要

Background Hypertension induces cardiac dysfunction, calcium (Ca 2 +) 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 (10 mg/kg for 4 weeks). 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.

原文英語
頁(從 - 到)5390-5395
頁數6
期刊International Journal of Cardiology
168
發行號6
DOIs
出版狀態已發佈 - 十月 15 2013

ASJC Scopus subject areas

  • 心臟病學與心血管醫學

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