Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo

Zhong, Peng; Quan, Dajun; Peng, Jianye; Xiong, Xiaoju; Liu, Yu; Kong, Bin; Huang, He

doi:10.1016/j.yjmcc.2017.06.010

Cited by 41 publications

(25 citation statements)

References 63 publications

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“…Besides Ca 2+ /calmodulin, CaMKII could also be activated by phosphorylation and oxidation [19–21]. Sustained excessive CaMKII activation has adverse effects on a variety of heart diseases [22, 23]. Some studies have found that CaMKII activity bloomed at the beginning of MIRI, which promoted calcium extravasation of the sarcoplasmic reticulum and aggravated myocardial dysfunction and injury [24, 25].…”

Section: Introductionmentioning

confidence: 99%

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca²⁺/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

Luo

Shen

Chen

et al. 2019

Oxidative Medicine and Cellular Longevity

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Ca2+/calmodulin-dependent protein kinase II (CaMKII), regulated by inhibitor 1 of protein phosphatase 1 (I1PP1), is vital for maintaining cardiovascular homeostasis. However, the role and mechanism of I1PP1 against hypoxia-reoxygenation (H/R) injury in cardiomyocytes remain a question. In our study, after I1PP1 overexpression by adenovirus infection in the neonatal cardiomyocytes followed by hypoxia for 4 h and reoxygenation for 12 h, the CaMKIIδ alternative splicing subtype, ATP content, and lactate dehydrogenase (LDH) release were determined. CaMKII activity was evaluated by phosphoprotein phosphorylation at Thr17 (p-PLB Thr17), CaMKII phosphorylation (p-CaMKII), and CaMKII oxidation (ox-CaMKII). Reactive oxygen species (ROS), mitochondrial membrane potential, dynamin-related protein 1 (DRP1), and optic atrophy 1 (OPA1) expressions were assessed. Our study verified that I1PP1 overexpression attenuated the CaMKIIδ alternative splicing disorder; suppressed PLB phosphorylation at Thr17, p-CaMKII, and ox-CaMKII; decreased cell LDH release; increased ATP content; attenuated ROS production; increased mitochondrial membrane potential; and decreased DRP1 expression but increased OPA1 expression in the cardiomyocytes after H/R. Contrarily, CaMKIIδ alternative splicing disorder, LDH release, ATP reduction, and ROS accumulation were aggravated after H/R injury with the I1PP1 knockdown. Collectively, I1PP1 overexpression corrected disorders of CaMKIIδ alternative splicing, inhibited CaMKII phosphorylation, repressed CaMKII oxidation, suppressed ROS production, and attenuated cardiomyocyte H/R injury.

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Section: Introductionmentioning

confidence: 99%

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca²⁺/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

Luo

Shen

Chen

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Given the above results, we then examined a mediator that connects TRPV1-evoked Ca 2+ influx and the Nrf2 nuclear localization. Given that CaMKII is a major Ca 2+ signal transducer involved in a variety of signaling pathways 35 , 36 , we reasoned that CaMKII might be the mediator between Ca 2+ signaling and Nrf2. We harvested proteins of RAW264.7 cells after 5-, 15-, and 30-min LPS induction with or without CPS treatment.…”

Section: Resultsmentioning

confidence: 99%

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

Sun

et al. 2021

Cell Death Dis

102

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Osteoarthritis (OA) is the major course of joint deterioration, in which M1 macrophage-driven synovitis exacerbates the pathological process. However, precise therapies for M1 macrophage to decrease synovitis and attenuate OA progression have been scarcely proposed. Transient receptor potential vanilloid 1 (TRPV1) is a cation channel that has been implicated in pain perception and inflammation. In this study, we investigated the role of TRPV1 in the M1 macrophage polarization and pathogenesis of OA. We demonstrated that TRPV1 expression and M1 macrophage infiltration were simultaneously increased in both human and rat OA synovium. More than 90% of the infiltrated M1 macrophages expressed TRPV1. In the rat OA model, intra-articular injection of capsaicin (CPS), a specific TRPV1 agonist, significantly attenuated OA phenotypes, including joint swelling, synovitis, cartilage damage, and osteophyte formation. CPS treatment markedly reduced M1 macrophage infiltration in the synovium. Further mechanistic analyses showed that TRPV1-evoked Ca2+ influx promoted the phosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and facilitated the nuclear localization of nuclear factor-erythroid 2-related factor 2 (Nrf2), which ultimately resulted in the inhibition of M1 macrophage polarization. Taken together, our findings establish that TRPV1 attenuates the progression of OA by inhibiting M1 macrophage polarization in synovium via the Ca2+/CaMKII/Nrf2 signaling pathway. These results highlight the effect of targeting TRPV1 for the development of a promising therapeutic strategy for OA.

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“…Additionally, the activation of CaMKII in cardiomyocytes triggers the activation of NF‐κB and the expression of inflammatory chemokines and cytokines and ultimately increased AF vulnerability . Several studies have demonstrated that CaMKII can regulate NF‐κB activation under pathological conditions, such as myocardial infarction, ischaemia/reperfusion injury, and obesity, which suggests that CaMKII serves to trigger and sustain subsequent changes in inflammatory gene expression that contribute to cardiac stress . Our previous studies showed that MD1 deletion leads to a more pronounced activation of the TLR4/CaMKII signalling pathway, which may further significantly influence the expression levels of Ca 2+ handling proteins, increasing the vulnerability of HF mice to ventricular arrhythmia .…”

Section: Discussionmentioning

confidence: 99%

Loss of myeloid differentiation protein 1 promotes atrial fibrillation in heart failure with preserved ejection fraction

et al. 2020

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Aims Myeloid differentiation protein 1 (MD1) is expressed in the mammalian heart and exerts an anti-arrhythmic effect. Atrial fibrillation (AF) is closely related to heart failure with preserved ejection fraction (HFpEF). The potential impact of MD1 on AF vulnerability in an HFpEF model is not clear. Methods and results MD1 knock-out and wild-type (WT) mice were subjected to uninephrectomy and continuous saline or D-aldosterone infusion and given 1% sodium chloride drinking water for 4 weeks. Echocardiographic and haemodynamic measurements, electrophysiological studies, Masson staining, and molecular analysis were performed. Aldosterone-infused WT mice develop HFpEF with left ventricular hypertrophy, moderate hypertension, pulmonary congestion, and diastolic dysfunction. Aldosterone infusion increased the vulnerability of WT mice to AF, as shown by a prolonged interatrial conduction time, shortened effective refractory period, and higher incidence of AF. In addition, aldosterone infusion increased myocardial fibrosis and inflammation, decreased sarcoplasmic reticulum Ca 2+ -ATPase 2a protein expression and the phosphorylation of phospholamban at Thr17, and increased sodium/calcium exchanger 1 protein expression and the phosphorylation of ryanodine receptor 2 in WT mice. All of the above adverse effects of aldosterone infusion were further exacerbated in MD1 knock-out mice compare with WT mice. Mechanistically, MD1 deletion increased the activation of the toll-like receptor 4/calmodulindependent protein kinase II signalling pathway in in vivo and in vitro experiments. Conclusions MD1 deficiency increases the vulnerability of HFpEF mice to AF. This is mainly caused by aggravated maladaptive left atrial fibrosis and inflammation and worsened dysregulation of calcium handling, which is induced by the enhanced activation of the toll-like receptor 4/calmodulin-dependent protein kinase II signalling pathway.

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Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo

Cited by 41 publications

References 63 publications

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca²⁺/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca²⁺/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

Loss of myeloid differentiation protein 1 promotes atrial fibrillation in heart failure with preserved ejection fraction

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Role of CaMKII in free fatty acid/hyperlipidemia-induced cardiac remodeling both in vitro and in vivo

Cited by 41 publications

References 63 publications

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca2+/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca2+/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

TRPV1 alleviates osteoarthritis by inhibiting M1 macrophage polarization via Ca2+/CaMKII/Nrf2 signaling pathway

Loss of myeloid differentiation protein 1 promotes atrial fibrillation in heart failure with preserved ejection fraction

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Inhibitor 1 of Protein Phosphatase 1 Regulates Ca²⁺/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes

Inhibitor 1 of Protein Phosphatase 1 Regulates Ca²⁺/Calmodulin-Dependent Protein Kinase II to Alleviate Oxidative Stress in Hypoxia-Reoxygenation Injury of Cardiomyocytes