Inhibition of Ca2+-dependent protein kinase C rescues high calcium–induced pro-arrhythmogenic cardiac alternans in rabbit hearts

Zhang, Peipei; Hu, Long; Tian, Yan; Zhang, Zefu; Zhang, Peihua; Yang, Yanyan; Li, Shi-Han; Ma, Jing

doi:10.1007/s00424-021-02574-7

Cited by 3 publications

(2 citation statements)

References 37 publications

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“…Calcium overload directly activates PKC-β by recruiting its C2 domain to the cellular membrane, therefore promoting the development of pro-arrhythmogenic cardiac alternants in rabbit hearts [ 23 , 24 ]. To explore the functional relationship between cytosolic Ca 2+ and oxidative stress in HCAECs, 0.2 μM ionomycin (IONO) was applied to enhance intracellular Ca 2+ ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Empagliflozin prevents oxidative stress in human coronary artery endothelial cells via the NHE/PKC/NOX axis

Li,

Wang,

Kalina

et al. 2024

Redox Biology

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Section: Resultsmentioning

confidence: 99%

Empagliflozin prevents oxidative stress in human coronary artery endothelial cells via the NHE/PKC/NOX axis

Li,

Wang,

Kalina

et al. 2024

Redox Biology

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“…Currently, it is often said that the Ca 2+ current in cardiac myocytes mainly refers to the I Ca-L generated by the opening of L-type Ca 2+ channels (Bers, 2002). Ca 2+ overload in pathological conditions is strongly associated with arrhythmias, cardiac hypertrophy and heart failure (Markandeya et al, 2015;Santulli, Xie, Reiken, & Marks, 2015;Zhang et al, 2021). Therefore, intracellular Ca 2+ homeostasis is important for the maintenance of normal heart physiological function (Barry & Bridge, 1993).…”

Section: Discussionmentioning

confidence: 99%

The cardioprotective effects and mechanisms of naringenin in myocardial ischemia based on network pharmacology and experiment verification

Yang

Chen

et al. 2022

Front. Pharmacol.

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Naringenin (Nar) is a natural flavonoid extracted from citrus fruits with abundant pharmacological properties against cardiac diseases, but existing studies are unsystematic and scattered. The present research systematically investigates the mechanism of action of Nar in the treatment of myocardial ischemia (MI). Network pharmacology was used to analyze the relevant targets of Nar against MI as well as the biological mechanisms. The protective effect of Nar was initially assessed in H9c2 cells induced by CoCl2. In acutely isolated rat cardiomyocytes, Nar was further explored for effects on L-type Ca2+ currents, cell contractility and Ca2+ transients by using patch-clamp technique and Ion Optix system. Network pharmacology analysis indicated that Nar improved apoptosis, mitochondrial energy metabolism, inflammation and oxidative stress. Experimental validation demonstrated that Nar decreased ROS and MDA levels and increased antioxidant activity (e.g., GSH-PX, SOD, and CAT), mitochondrial membrane potential, ATP and Ca2+-ATPase contents. Nar also markedly reduced inflammatory factor levels, apoptosis, and intracellular Ca2+ concentrations in H9c2 cells. Based on the experimental results, it is speculated that Ca2+ signals play an essential role in the process of Nar against MI. Thus, we further confirmed that Nar significantly inhibited the L-type Ca2+ currents, contractility and Ca2+ transients in acutely isolated cardiomyocytes. The inhibition of Ca2+ overload by Nar may be a novel cardioprotective mechanism. The present study may serve as a basis for future clinical research, and Nar as a Ca2+ channel inhibitor may provide new perspectives for the treatment of myocardial ischemic diseases.

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Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death

et al. 2023

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Background and Aims The ryanodine receptor (RyR2) is essential for cardiac muscle excitation-contraction coupling, dysfunctional RyR2 participates in the development of inherited arrhythmogenic cardiac disease. In this study, a novel RyR2 mutation A690E is identified from a patient with family inheritance of sudden cardiac death, and we investigated the pathogenic basis of the mutation. Methods and Results We generated a mouse model that carried the A690E mutation. Mice were characterized by adrenergic-induced ventricular arrhythmias similar to clinical manifestation of the patient. Optical mapping studies revealed that isolated A690E hearts were prone to arrhythmogenesis and displayed frequency-dependence calcium transient alternans. Upon β-adrenoceptor challenge, the concordant alternans was shifted towards discordant alternans that favor triggering ectopic beats and Ca2+ re-entry, similar phenomenon was also found in the A690E cardiomyocytes. In addition, we found that A690E cardiomyocytes manifested abnormal Ca2+ release and electrophysiological disorders, including an increased sensitivity to cytosolic Ca2+, an elevated diastolic RyR2-mediated Ca2+ leak, and an imbalance between Ca2+ leak and reuptake. Structural analyses reveal that the mutation directly impacts RyR2-FKBP interaction. Conclusions In this study, we have identified a novel mutation in RyR2 that is associated with sudden cardiac death. By characterizing the function defects of mutant RyR2 in animal, whole heat, and cardiomyocytes, we demonstrated the pathogenic basis of the disease-causing mutation and provided a deeper mechanistic understanding of a life-threatening cardiac arrhythmia.

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Inhibition of Ca2+-dependent protein kinase C rescues high calcium–induced pro-arrhythmogenic cardiac alternans in rabbit hearts

Cited by 3 publications

References 37 publications

Empagliflozin prevents oxidative stress in human coronary artery endothelial cells via the NHE/PKC/NOX axis

Empagliflozin prevents oxidative stress in human coronary artery endothelial cells via the NHE/PKC/NOX axis

The cardioprotective effects and mechanisms of naringenin in myocardial ischemia based on network pharmacology and experiment verification

Arrhythmogenic mechanism of a novel ryanodine receptor mutation underlying sudden cardiac death

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