Electrophysiological basis of metabolic-syndrome-induced cardiac dysfunction

Okatan, Esma N.; Durak, Ayşegül; Turan, Belma

doi:10.1139/cjpp-2015-0531

Cited by 29 publications

(42 citation statements)

References 45 publications

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“…In this regard, previous studies using highsucrose diets have shown marked glucose intolerance in experimental animals (Brenner et al 2003;Sumiyoshi et al 2006), which is supported due to previously shown data on an association with promotion of insulin signaling and high H 2 O 2 giving a fact on typical metabolic actions of insulin linking to ROS and insulin relation (Czech et al 1974). It seems that oxidation-induced disruption of cellular redistributed signaling molecules in response to insulin stimulation is associated with impaired insulin action in case of many pathological conditions such as obesity The clustering of metabolic abnormality is closely related to the progression of cardiovascular disorders (Balderas-Villalobos et al 2013;Merabet et al 2015;Okatan et al 2016). Indeed, a correlation between obesity, insulin resistance and contractile dyfunction at most due to defect in intracellular Ca 2+ handling in rat heart with MetS have been observed, previously (Balderas-Villalobos et al 2013;Nevelsteen et al 2013).…”

Section: R a F Tsupporting

confidence: 52%

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats

Durak

Olğar

Tuncay

et al. 2017

Can. J. Physiol. Pharmacol.

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Mechanical activity of the heart is adversely affected with metabolic syndrome (MetS) characterized with increased body-mass and marked insulin-resistance.Herein, we examined effects of high-carbohydrate intake on cardiac functional abnormalities via evaluating in situ heart-work, heart-rate and electrocardiograms (ECG) in rats. MetS is induced in Wistar male rats by adding 32% sucrose for 22-24 weeks and confirmed with insulin-resistance, increased body-weight, blood glucose and insulin, systolic and diastolic blood pressures besides significant left ventricular integrity-lost and increased connective-tissue around myofibrils. Analysis of in situ ECG-recordings showed markedly shorten QT-interval and depressed QRP with increased heart-rate. We also observed augmented oxidative stress and decreased antioxidant defense characterized with decreases in serum total thiol-level and attenuated paraoxonase and arylesterase activities. Our data clearly indicate that increased heart-rate and shortened QT-interval concomitant with higher left ventricular developed pressure responses to β-adrenoreceptor stimulation as a result of less cAMP-release could be regarded as natural compensation mechanisms in overweight MetS rats. Since MetS leads further to persistent insulin-resistance and obesity, one should get into consideration these important facts associated with onset of the depressed heart-work, the increased heart-rate and shorten QT-interval in highcarbohydrate intake, which will possible lead to more deleterious effects on mammalian heart.

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Section: R a F Tsupporting

confidence: 52%

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats

Durak

Olğar

Tuncay

et al. 2017

Can. J. Physiol. Pharmacol.

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“…In a prediabetic model of metabolic syndrome, whereby dogs were chronically fed a high fat diet (HFD), phosphorylation of RyR2 at S2808 was significantly elevated and the channel’s ability to bind [ 3 H] ryanodine significantly depressed in the ventricles compared to healthy controls, while no changes in RyR2 mRNA or protein expression were observed ( Dinçer et al, 2006 ). Okatan et al (2016) also observed increased RyR2 phosphorylation at S2808 in rats with high sucrose diet-induced metabolic syndrome, accompanied by reduced FKBP12.6 expression. Through studies of electric-field stimulated intracellular Ca 2+ handling, cardiomyocytes isolated from rats with metabolic syndrome showed significantly increased SR Ca 2+ leak, depressed SR Ca 2+ loading and reduced Ca 2+ transient amplitude vs. controls.…”

Section: The Ryanodine Receptormentioning

confidence: 63%

Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity

Hamilton

Terentyev

2018

Front. Physiol.

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A rapid growth in the incidence of diabetes and obesity has transpired to a major heath issue and economic burden in the postindustrial world, with more than 29 million patients affected in the United States alone. Cardiovascular defects have been established as the leading cause of mortality and morbidity of diabetic patients. Over the last decade, significant progress has been made in delineating mechanisms responsible for the diminished cardiac contractile function and enhanced propensity for malignant cardiac arrhythmias characteristic of diabetic disease. Rhythmic cardiac contractility relies upon the precise interplay between several cellular Ca2+ transport protein complexes including plasmalemmal L-type Ca2+ channels (LTCC), Na+-Ca2+ exchanger (NCX1), Sarco/endoplasmic Reticulum (SR) Ca2+-ATPase (SERCa2a) and ryanodine receptors (RyR2s), the SR Ca2+ release channels. Here we provide an overview of changes in Ca2+ homeostasis in diabetic ventricular myocytes and discuss the therapeutic potential of targeting Ca2+ handling proteins in the prevention of diabetes-associated cardiomyopathy and arrhythmogenesis.

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“…In another set of experiments, to evaluate and compare the SERCA function in β 3 ‐AR stimulated cells, we examined SR Ca 2+ leak, as described elsewhere (Okatan, Durak, & Turan, ). Figure c (inset) shows an example of measurement of SR Ca 2+ leak in cardiomyocytes at room temperature.…”

Section: Resultsmentioning

confidence: 99%

β₃‐adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn²⁺ and reactive nitrogen species

Tuncay

Olğar

Durak

et al. 2019

Journal Cellular Physiology

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Role of β3‐AR dysregulation, as either cardio‐conserving or cardio‐disrupting mediator, remains unknown yet. Therefore, we examined the molecular mechanism of β3‐AR activation in depressed myocardial contractility using a specific agonist CL316243 or using β3‐AR overexpressed cardiomyocytes. Since it has been previously shown a possible correlation between increased cellular free Zn2+ ([Zn2+]i) and depressed cardiac contractility, we first demonstrated a relation between β3‐AR activation and increased [Zn2+]i, parallel to the significant depolarization in mitochondrial membrane potential in rat ventricular cardiomyocytes. Furthermore, the increased [Zn2+]i induced a significant increase in messenger RNA (mRNA) level of β3‐AR in cardiomyocytes. Either β3‐AR activation or its overexpression could increase cellular reactive oxygen species (ROS) and reactive nitrogen species (RNS) levels, in line with significant changes in nitric oxide (NO)‐pathway, including increases in the ratios of pNOS3/NOS3 and pGSK‐3β/GSK‐3β, and PKG expression level in cardiomyocytes. Although β3‐AR activation induced depression in both Na+‐ and Ca2+‐currents, the prolonged action potential (AP) seems to be associated with a marked depression in K+‐currents. The β3‐AR activation caused a negative inotropic effect on the mechanical activity of the heart, through affecting the cellular Ca2+‐handling, including its effect on Ca2+‐leakage from sarcoplasmic reticulum (SR). Our cellular level data with β3‐AR agonism were supported with the data on high [Zn2+]i and β3‐AR protein‐level in metabolic syndrome (MetS)‐rat heart. Overall, our present data can emphasize the important deleterious effect of β3‐AR activation in cardiac remodeling under pathological condition, at least, through a cross‐link between β3‐AR activation, NO‐signaling, and [Zn2+]i pathways. Moreover, it is interesting to note that the recovery in ER‐stress markers with β3‐AR agonism in hyperglycemic cardiomyocytes is favored. Therefore, how long and to which level the β3‐AR agonism would be friend or become foe remains to be mystery, yet.

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Electrophysiological basis of metabolic-syndrome-induced cardiac dysfunction

Cited by 29 publications

References 45 publications

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats

Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity

β₃‐adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn²⁺ and reactive nitrogen species

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Electrophysiological basis of metabolic-syndrome-induced cardiac dysfunction

Cited by 29 publications

References 45 publications

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats

Onset of decreased heart work is correlated with increased heart rate and shortened QT interval in high-carbohydrate fed overweight rats

Proarrhythmic Remodeling of Calcium Homeostasis in Cardiac Disease; Implications for Diabetes and Obesity

β3‐adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn2+ and reactive nitrogen species

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β₃‐adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn²⁺ and reactive nitrogen species