TY - JOUR
T1 - The dipeptidyl peptidase-4 inhibitor-sitagliptin modulates calcium dysregulation, inflammation, and PPARs in hypertensive cardiomyocytes
AU - Lee, T. I.
AU - Kao, Y. H.
AU - Chen, Y. C.
AU - Huang, J. H.
AU - Hsu, M. I.
AU - Chen, Y. J.
N1 - Funding Information:
The present work was supported by grants from Taipei Medical University, Wan Fang Hospital ( 102-wf-eva-01 and 101-wf-eva-02 ), and the National Science Council, Taiwan ( NSC100-2325-B-010-005 and NSC101-2325-B-010-005 ). The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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.
AB - 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.
KW - Calcium handling
KW - Cardiomyocytes
KW - DPP-4 inhibitor
KW - Hypertension
KW - Sitagliptin
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U2 - 10.1016/j.ijcard.2013.08.051
DO - 10.1016/j.ijcard.2013.08.051
M3 - Article
C2 - 24012160
AN - SCOPUS:84887202275
SN - 0167-5273
VL - 168
SP - 5390
EP - 5395
JO - International Journal of Cardiology
JF - International Journal of Cardiology
IS - 6
ER -