Receptor activator of nuclear factor-κB ligand is a novel inducer of myocardial inflammation

Ock, Sangmi; Ahn, Jeongmin; Lee, Seok Hong; Park, Hongryeol; Son, Jang Won; Oh, Jae Gyun; Yang, Dong Kwon; Lee, Wang Soo; Kim, Ho Shik; Rho, Jaerang; Oh, Goo Taeg; Abel, E. Dale; Park, Woo Jin; Kim, Jung Min; Kim, Jaetaek

doi:10.1093/cvr/cvs078

Cited by 47 publications

(26 citation statements)

References 37 publications

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“…Echocardiography was performed using the Vevo 770 System (VisualSonics Inc., Toronto, Ontario, Canada) with a 30-MHz transducer in the 2-dimensional M-mode [13]. …”

Section: Methodsmentioning

confidence: 99%

“…Western blotting analysis was performed as described previously [13]. Mouse hearts or neonatal rat cardiomyocytes (NRCMs) were lysed with lysis buffer (20 mM Tris-HCl, pH 7.4; 1% Triton X-100; 1 mM EDTA; 30 mM HEPES; 50 mM Na 4 P 2 O 7 ; 100 mM NaF) containing 1× Protease Inhibitor Cocktail (Roche Molecular Biochemicals, Indianapolis, IN, USA) and phosphatase inhibitors.…”

Section: Methodsmentioning

confidence: 99%

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Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that correlate with cardiac contractile dysfunction in Akt deficient hearts

Ock

Lee

Kim

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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While deletion of Akt1 results in a smaller heart size and Akt2 mice are mildly insulin resistant, Akt1/Akt2 mice exhibit perinatal lethality, indicating a large degree of functional overlap between the isoforms of the serine/threonine kinase Akt. The present study aimed to determine the cooperative contribution of Akt1 and Akt2 on the structure and contractile function of adult hearts. To generate an inducible, cardiomyocyte-restricted Akt2 knockout (KO) model, Akt2 mice were crossed with tamoxifen-inducible MerCreMer transgenic (MCM) mice and germline Akt1 mice to generate the following genotypes:Akt1; Akt2 (WT), Akt2; α-MHC-MCM (iAkt2 KO), Akt1, and Akt1; Akt2; α-MHC-MCM mice (Akt1/iAkt2 KO). At 28 days after the first tamoxifen injection, Akt1/iAkt2 KO mice developed contractile dysfunction paralleling increased atrial and brain natriuretic peptide (ANP and BNP) levels, and repressed mitochondrial gene expression. Neither cardiac fibrosis nor apoptosis were detected in Akt1/iAkt2 KO hearts. To explore potential molecular mechanisms for contractile dysfunction, we investigated myocardial microstructure before the onset of heart failure. At 3 days after the first tamoxifen injection, Akt1/iAkt2 KO hearts showed decreased expression of connexin43 (Cx43) and connexin-interacting protein zonula occludens-1 (ZO-1). Furthermore, Akt1/2 silencing significantly decreased both Cx43 and ZO-1 expression in cultured neonatal rat cardiomyocytes in concert with reduced beating frequency. Akt1 and Akt2 are required to maintain cardiac contraction. Loss of Akt signaling disrupts gap junction protein, which might precipitate early contractile dysfunction prior to heart failure in the absence of myocardial remodeling, such as hypertrophy, fibrosis, or cell death.

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“…Echocardiography was performed using the Vevo 770 System (VisualSonics Inc., Toronto, Ontario, Canada) with a 30-MHz transducer in the 2-dimensional M-mode [13]. …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that correlate with cardiac contractile dysfunction in Akt deficient hearts

Ock

Lee

Kim

et al. 2018

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…A flow cytometer was used to determine the uptake of DOX into the MCF‐7/ADR cells . MCF‐7/ADR cells were seeded into six‐well plates overnight to allow them to adhere at the bottom of the plate.…”

Section: Methodsmentioning

confidence: 99%

Drug resistance reversal by combretastatin-A4 phosphate loaded with doxorubicin in polymersomes independent of angiogenesis effect

Zhu

Qiu

2017

Journal of Pharmacy and Pharmacology

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“…A role for elevated NF-κB in HF is also supported by the study of Ock et al . [68], showing that raising NF-κB by lowering RANKL levels produces a substantial myocardial inflammatory effect, including raised levels of TNF-α and IL-1β. del Vescovo et al .…”

Section: Role Of Elevated No/onoo-cycle Elements In Hfmentioning

confidence: 99%

The NO/ONOO-Cycle as the Central Cause of Heart Failure

Pall

2013

IJMS

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The NO/ONOO-cycle is a primarily local, biochemical vicious cycle mechanism, centered on elevated peroxynitrite and oxidative stress, but also involving 10 additional elements: NF-κB, inflammatory cytokines, iNOS, nitric oxide (NO), superoxide, mitochondrial dysfunction (lowered energy charge, ATP), NMDA activity, intracellular Ca2+, TRP receptors and tetrahydrobiopterin depletion. All 12 of these elements have causal roles in heart failure (HF) and each is linked through a total of 87 studies to specific correlates of HF. Two apparent causal factors of HF, RhoA and endothelin-1, each act as tissue-limited cycle elements. Nineteen stressors that initiate cases of HF, each act to raise multiple cycle elements, potentially initiating the cycle in this way. Different types of HF, left vs. right ventricular HF, with or without arrhythmia, etc., may differ from one another in the regions of the myocardium most impacted by the cycle. None of the elements of the cycle or the mechanisms linking them are original, but they collectively produce the robust nature of the NO/ONOO-cycle which creates a major challenge for treatment of HF or other proposed NO/ONOO-cycle diseases. Elevated peroxynitrite/NO ratio and consequent oxidative stress are essential to both HF and the NO/ONOO-cycle.

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Receptor activator of nuclear factor-κB ligand is a novel inducer of myocardial inflammation

Abstract: Our data demonstrate for the first time that the pressure-overloaded myocardium generates RANKL, which induces TNF-α, IL-1α, and IL-1β production via a RANK-TRAF2/TRAF6-PLC-PKC-NF-κB-mediated autocrine mechanism.

Cited by 47 publications

References 37 publications

Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that correlate with cardiac contractile dysfunction in Akt deficient hearts

Connexin43 and zonula occludens-1 are targets of Akt in cardiomyocytes that correlate with cardiac contractile dysfunction in Akt deficient hearts

Drug resistance reversal by combretastatin-A4 phosphate loaded with doxorubicin in polymersomes independent of angiogenesis effect

The NO/ONOO-Cycle as the Central Cause of Heart Failure

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