STIM1-Orai1 interaction mediated calcium influx activation contributes to cardiac contractility of insulin-resistant rats.

Purpose: Metabolic syndrome (MetS) became a tremendous public health burden in the last decades. Store-operated calcium entry (SOCE) is a unique mechanism that causes a calcium influx, which is triggered by calcium store depletion. MetS-induced alterations in cardiac calcium signaling, especially in SOCE are still unclear.

Ticagrelor alleviates high-carbohydrate intake induced altered electrical activity of ventricular cardiomyocytes by regulating sarcoplasmic reticulum-mitochondria miscommunication.

Metabolic syndrome (MetS) is associated with additional cardiovascular risk in mammalians while there are relationships between hyperglycemia-associated cardiovascular dysfunction and increased platelet P2Y12 receptor activation. Although P2Y12 receptor antagonist ticagrelor (Tica) plays roles in reduction of cardiovascular events, its beneficial mechanism remains poorly understood. Therefore, we aimed to clarify whether Tica can exert a direct protective effect in ventricular cardiomyocytes from high-carbohydrate diet-induced MetS rats, at least, through affecting sarcoplasmic reticulum (SR)-mitochondria (Mit) miscommunication.

Interrelated In Vitro Mechanisms of Sibutramine-Induced Cardiotoxicity.

Consumption of illicit pharmaceutical products containing sibutramine has been reported to cause cardiovascular toxicity problems. This study aimed to demonstrate the toxicity profile of sibutramine, and thereby provide important implications for the development of more effective strategies in both clinical approaches and drug design studies. Action potentials (APs) were determined from freshly isolated ventricular cardiomyocytes with whole-cell configuration of current clamp as online.

Ageing-associated increase in SGLT2 disrupts mitochondrial/sarcoplasmic reticulum Ca homeostasis and promotes cardiac dysfunction.

The prevalence of death from cardiovascular disease is significantly higher in elderly populations; the underlying factors that contribute to the age-associated decline in cardiac performance are poorly understood. Herein, we identify the involvement of sodium/glucose co-transporter gene (SGLT2) in disrupted cellular Ca -homeostasis, and mitochondrial dysfunction in age-associated cardiac dysfunction. In contrast to younger rats (6-month of age), older rats (24-month of age) exhibited severe cardiac ultrastructural defects, including deformed, fragmented mitochondria with high electron densities.

β -adrenergic receptor activation plays an important role in the depressed myocardial contractility via both elevated levels of cellular free Zn and reactive nitrogen species.

Role of β -AR dysregulation, as either cardio-conserving or cardio-disrupting mediator, remains unknown yet. Therefore, we examined the molecular mechanism of β -AR activation in depressed myocardial contractility using a specific agonist CL316243 or using β -AR overexpressed cardiomyocytes. Since it has been previously shown a possible correlation between increased cellular free Zn ([Zn ] ) and depressed cardiac contractility, we first demonstrated a relation between β -AR activation and increased [Zn ] , parallel to the significant depolarization in mitochondrial membrane potential in rat ventricular cardiomyocytes.

A SGLT2 inhibitor dapagliflozin suppresses prolonged ventricular-repolarization through augmentation of mitochondrial function in insulin-resistant metabolic syndrome rats.

Background: Metabolic syndrome (MetS) is a prevalent risk factor for cardiac dysfunction. Although SGLT2-inhibitors have important cardioprotective effects in hyperglycemia, their underlying mechanisms are complex and not completely understood. Therefore, we examined mechanisms of a SGLT2-inhibitor dapagliflozin (DAPA)-related cardioprotection in overweight insulin-resistant MetS-rats comparison with insulin (INSU), behind its glucose-lowering effect.

Aging related functional and structural changes in the heart and aorta: MitoTEMPO improves aged-cardiovascular performance.

Aging in humans represents declining in cardio-protective systems, however its mechanisms are not known yet. We aimed to analyse how aging affects key mechanisms responsible for contractile dysfunction via comparing the improperly synchrony between electrical and mechanical activities in male aged-rats (24-month old) comparison to those of adult-rats (6-month old). We determined significantly increased systemic oxidative stress with decreased antioxidant capacity, clear insulin resistance and hypertrophy in aged-rats with normal fasting blood glucose.

Cytosolic increased labile Zn contributes to arrhythmogenic action potentials in left ventricular cardiomyocytes through protein thiol oxidation and cellular ATP depletion.

Intracellular labile (free) Zn-level ([Zn]) is low and increases markedly under pathophysiological conditions in cardiomyocytes. High [Zn] is associated with alterations in excitability and ionic-conductances while exact mechanisms are not clarified yet. Therefore, we examined the elevated-[Zn] on some sarcolemmal ionic-mechanisms, which can mediate cardiomyocyte dysfunction.

Interplay Between Cytosolic Free Zn and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.

The Zn in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO (extracellular exposure) or Zn pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner.