Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage

Rennison, Julie H.; Li, Ling; Lin, Cheryl R; Lovano, Beth; Castel, Laurie; Wass, Sojin Youn; Cantlay, Catherine; McHale, Meghan; Gillinov, A. Marc; Mehra, Reena; Willard, Belinda; Smith, Jonathan; Chung, Mina K.; Barnard, John; Wagoner, David R. Van

doi:10.1007/s00424-021-02514-5

Cited by 21 publications

(17 citation statements)

References 52 publications

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“…A similar downregulation was reported in prevalent AF. It was suggested that AF causes increased energy demands initiating an uncoordinated response and increased tissue inhomogeneity 23 . We observed J o u r n a l P r e -p r o o f decreased energy metabolism preceding AF, suggesting this process is not the result of AF itself.…”

Section: Metabolic Pathways Are Downregulatedmentioning

confidence: 99%

Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial

et al. 2021

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Metabolic Pathways Are Downregulatedmentioning

confidence: 99%

Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial

et al. 2021

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“…Accordingly, mitoK-ATP is the final effector of cardioprotective strategies in acute IR injury and in preclinical models of diabetic and hypertrophic cardiomyopathy [ 8 , 9 , 10 , 22 ]. Moreover, in arrhythmic patients, a significant reduction in mitoK-ATP expression is associated with an increased atrial fibrillation rate [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression

Canale

Nicolini

Pitto

et al. 2022

IJMS

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The opening of the ATP-sensitive mitochondrial potassium channel (mitok-ATP) is a common goal of cardioprotective strategies in the setting of acute and chronic myocardial disease. The biologically active thyroid hormone (TH), 3-5-3-triiodothyronine (T3), has been indicated as a potential activator of mitoK-ATP but the underlying mechanisms are still elusive. Here we describe a novel role of T3 in the transcriptional regulation of mitoK and mitoSur, the recently identified molecular constituents of the channel. To mimic human ischemic heart damage, we used a rat model of a low T3 state as the outcome of a myocardial ischemia/reperfusion event, and neonatal rat cardiomyocytes (NRCM) challenged with hypoxia or H2O2. Either in the in vivo or in vitro models, T3 administration to recover the physiological concentrations was able to restore the expression level of both the channel subunits, which were found to be downregulated under the stress conditions. Furthermore, the T3-mediated transcriptional activation of mitoK-ATP in the myocardium and NRCM was associated with the repression of the TH-inactivating enzyme, deiodinase 3 (Dio3), and an up-regulation of the T3-responsive miR-133a-3p. Mechanistically, the loss and gain of function experiments and reporter gene assays performed in NRCM, have revealed a new regulatory axis whereby the silencing of Dio3 under the control of miR-133a-3p drives the T3-dependent modulation of cardiac mitoK and mitoSur transcription.

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“…Pathological conditions associated with congenital heart disease or ischemia/reperfusion are associated with re-expression of α-HC and atrial forms of the LCs in the ventricle and down-regulation of ventricular LCs [45][46][47][48]. As for the atria, very little is known, but upregulation of LC1v and LC2v and down-regulation of LC1a and LC2a, [49] have been reported in association with upregulation of β-HC in atrial fibrillation [50,51]. Overall, the expression of the HC and related LCs appear then to be closely coordinated.…”

Section: Myosin Isoforms In the Heartmentioning

confidence: 99%

“…Atrial fibrillation caused a significant increase in the relative amount of the slow β-HC expressed by the human atrial myocardium compared to control conditions (from 10–25% to 40–50%, [ 141 ]) which could directly account for the observed marked reduction in activation and relaxation kinetics observed in the myofibrils from atrial fibrillation patients [ 31 ], in association with the parallel shift of LC1 and LC2 expression from the ventricular to atrial forms [ 49 , 50 ]. The negative impact of the HC isoform change on the power output and velocity of atrial contraction may then contribute to the atrial contractile dysfunction observed in atrial fibrillation, in the rather complex picture of alterations of gene expression observed in human atrial fibrillation at the proteomic and metabolomics levels [ 51 ].…”

Section: Myofibrils/myocytes Expressing α- Vs β-Myosinmentioning

confidence: 99%

Alpha and beta myosin isoforms and human atrial and ventricular contraction

Walklate

Ferrantini

Johnson

et al. 2021

Cell. Mol. Life Sci.

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Human atrial and ventricular contractions have distinct mechanical characteristics including speed of contraction, volume of blood delivered and the range of pressure generated. Notably, the ventricle expresses predominantly β-cardiac myosin while the atrium expresses mostly the α-isoform. In recent years exploration of the properties of pure α- & β-myosin isoforms have been possible in solution, in isolated myocytes and myofibrils. This allows us to consider the extent to which the atrial vs ventricular mechanical characteristics are defined by the myosin isoform expressed, and how the isoform properties are matched to their physiological roles. To do this we Outline the essential feature of atrial and ventricular contraction; Explore the molecular structural and functional characteristics of the two myosin isoforms; Describe the contractile behaviour of myocytes and myofibrils expressing a single myosin isoform; Finally we outline the outstanding problems in defining the differences between the atria and ventricles. This allowed us consider what features of contraction can and cannot be ascribed to the myosin isoforms present in the atria and ventricles.

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Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage

Cited by 21 publications

References 52 publications

Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial

Extracellular matrix remodeling precedes atrial fibrillation: Results of the PREDICT-AF trial

Role of miR-133/Dio3 Axis in the T3-Dependent Modulation of Cardiac mitoK-ATP Expression

Alpha and beta myosin isoforms and human atrial and ventricular contraction

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