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

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Abstract

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.

Original languageEnglish
Pages (from-to)5390-5395
Number of pages6
JournalInternational Journal of Cardiology
Volume168
Issue number6
DOIs
Publication statusPublished - Oct 15 2013

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Keywords

  • Calcium handling
  • Cardiomyocytes
  • DPP-4 inhibitor
  • Hypertension
  • Sitagliptin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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