Tumor Necrosis Factor-α in Heart Failure: an Updated Review

Schumacher, Sarah M.; Prasad, Sathyamangla V Naga

doi:10.1007/s11886-018-1067-7

Cited by 125 publications

(101 citation statements)

References 169 publications

(176 reference statements)

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“…TNF receptors (TNFRSF1A1 and TNFRSF1B) mediate the downstream cellular effects of TNF‐α, a pro‐inflammatory cytokine important for repair following tissue injury. However, persistent up‐regulation of TNF‐α leads to chronic inflammation and is implicated in cardiac dysfunction and HF …”

Section: Discussionmentioning

confidence: 94%

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic heart failure

Sama

Woolley

Nauta

et al. 2020

European J of Heart Fail

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Aims Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non‐ischaemic HF, it is important to better understand differences in underlying molecular mechanisms. Methods and results We performed a biological physical protein–protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT‐CHF study, 715 of whom had ischaemic HF and 445 had non‐ischaemic HF. Second, we constructed an enriched physical protein–protein interaction network, followed by a pathway over‐representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non‐ischaemic HF patients. We found 21/92 proteins to be up‐regulated and 2/92 down‐regulated in ischaemic relative to non‐ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin‐like growth factor binding protein‐1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort. Conclusions Pathophysiological pathways distinguishing patients with ischaemic HF from those with non‐ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF.

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Section: Discussionmentioning

confidence: 94%

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic heart failure

Sama

Woolley

Nauta

et al. 2020

European J of Heart Fail

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“…IL-1α and IL-1β activate a common IL-1 receptor (IL-1R), and seem via inflammation to be involved in a range of pathological processes [34][35][36]. In addition, TNF-α appears to be critical in the onset of pro-inflammatory signalling in silica-induced pathologies [37,38]. In contrast to larger crystalline silica particles that presumably exert their effects via such pro-inflammatory mediators, small SiNPs may translocate across the airway barrier to the systematic circulation, and potentially exert direct effects in secondary organs [39,40].…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

et al. 2020

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Background: Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression. Results: Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments. Conclusions: Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.

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“…In response to tissue injury, the heart activates the innate immune system to begin tissue repair mechanisms (Schumacher and Naga Prasad 2018), which are associated with the occurrence of significant increases in the levels of different pro-inflammatory cytokines (Braunwald 1997;Valen 2011;Mann 2015). This increase in pro-inflammatory cytokines aids in the process of cardiac remodeling and it has been suggested that this acute, proinflammatory stage is followed by an anti-inflammatory response to resolve the injury (Ionita et al 2010).…”

Section: Generation Of Pro-inflammatory Cytokinesmentioning

confidence: 99%

Mechanisms for the transition from physiological to pathological cardiac hypertrophy

Oldfield

Duhamel

Dhalla

2020

Can. J. Physiol. Pharmacol.

135

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The heart is capable of responding to stressful situations by increasing muscle mass, which is broadly defined as cardiac hypertrophy. This phenomenon minimizes ventricular wall stress for the heart undergoing a greater than normal workload. At initial stages, cardiac hypertrophy is associated with normal or enhanced cardiac function and is considered to be adaptive or physiological; however, at later stages, if the stimulus is not removed, it is associated with contractile dysfunction and is termed as pathological cardiac hypertrophy. It is during physiological cardiac hypertrophy where the function of subcellular organelles, including the sarcolemma, sarcoplasmic reticulum, mitochondria, and myofibrils, may be upregulated, while pathological cardiac hypertrophy is associated with downregulation of these subcellular activities. The transition of physiological cardiac hypertrophy to pathological cardiac hypertrophy may be due to the reduction in blood supply to hypertrophied myocardium as a consequence of reduced capillary density. Oxidative stress, inflammatory processes, Ca 2+ -handling abnormalities, and apoptosis in cardiomyocytes are suggested to play a critical role in the depression of contractile function during the development of pathological hypertrophy.Key words: cardiac hypertrophy, cardiac remodeling, pathological cardiac hypertrophy, physiological cardiac hypertrophy, adaptive cardiac hypertrophy, cardiac contractile function.Résumé : Le coeur est capable de réagir à des situations de stress par une augmentation de sa masse musculaire, que l'on caractérise plus largement comme étant de l'hypertrophie cardiaque. Ce phénomène permet de réduire au minimum la tension de la paroi ventriculaire dans un coeur soumis à une charge de travail plus élevée que normalement. Aux premiers stades, l'hypertrophie cardiaque est associée avec une fonction cardiaque normale ou améliorée et est considérée comme étant adaptative ou physiologique; toutefois, à des stades plus tardifs, si le stimulus n'est pas écarté, elle est associée avec un dysfonctionnement contractile et alors nommée hypertrophie cardiaque pathologique. C'est pendant l'hypertrophie cardiaque physiologique que le fonctionnement des organites sous-cellulaires, y compris le sarcolemme, le réticulum sarcoplasmique, les mitochondries et les myofibrilles peut être régulé à la hausse, tandis que l'hypertrophie cardiaque pathologique est associée avec une régulation à la baisse de ces activités sous-cellulaires. La transition de l'hypertrophie cardiaque physiologique vers l'hypertrophie cardiaque pathologique pourrait être le fait d'une diminution de l'apport sanguin au myocarde hypertrophié comme conséquence de la diminution de la densité des capillaires. On laisse entendre que le stress oxydatif, les processus inflammatoires, les anomalies de la gestion des ions Ca 2+ dans les cardiomyocytes ainsi que l'apoptose joueraient des rôles critiques dans la dépression de la fonction contractile au cours du développement de l'hypertrophie pathologique. [Traduit par...

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Tumor Necrosis Factor-α in Heart Failure: an Updated Review

Cited by 125 publications

References 169 publications

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic heart failure

A network analysis to identify pathophysiological pathways distinguishing ischaemic from non‐ischaemic heart failure

Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

Mechanisms for the transition from physiological to pathological cardiac hypertrophy

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