Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

Bakry, Samah A. El; Fayez, Dalia; Morad, Caroline S.; Abdelsalam, Ahmed M.; Abdel-Salam, Zeinab; Elkabarity, Rania Hamdy

doi:10.1016/j.cyto.2017.04.026

Cited by 12 publications

(9 citation statements)

References 34 publications

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“…These pathways were subsequently clustered into broader KEGG pathway categories. The most pronounced category was immune response, which included pathways such as chemokine and TLR signalling, while the most prominent correlation was to human ‘rheumatoid arthritis’ term, with known RA-related and cardiovascular disease-related genes ( Tnf , Il1b 37 and Acp5 38 ) being upregulated in both cell types. Other categories include cancer and infectious diseases, such as tuberculosis and pertussis which have also been associated with inflammation and TNF signalling.…”

Section: Resultsmentioning

confidence: 99%

Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis

et al. 2018

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ObjectivesPatients with rheumatoid arthritis and spondyloarthritisshow higher mortality rates, mainly caused by cardiac comorbidities. The TghuTNF (Tg197) arthritis model develops tumour necrosis factor (TNF)-driven and mesenchymalsynovial fibroblast (SF)-dependent polyarthritis. Here, we investigate whether this model develops, similarly to human patients, comorbid heart pathology and explore cellular and molecular mechanisms linking arthritis to cardiac comorbidities.MethodsHistopathological analysis and echocardiographic evaluation of cardiac function were performed in the Tg197 model. Valve interstitial cells (VICs) were targeted by mice carrying the ColVI-Cretransgene. Tg197 ColVI-Cre Tnfr1 fl/fl and Tg197 ColVI-Cre Tnfr1 cneo/cneo mutant mice were used to explore the role of mesenchymal TNF signalling in the development of heart valve disease. Pathogenic VICs and SFs were further analysed by comparative RNA-sequencing analysis.ResultsTg197 mice develop left-sided heart valve disease, characterised by valvular fibrosis with minimal signs of inflammation. Thickened valve areas consist almost entirely of hyperproliferative ColVI-expressing mesenchymal VICs. Development of pathology results in valve stenosis and left ventricular dysfunction, accompanied by arrhythmic episodes and, occasionally, valvular regurgitation. TNF dependency of the pathology was indicated by disease modulation following pharmacological inhibition or mesenchymal-specific genetic ablation or activation of TNF/TNFR1 signalling. Tg197-derived VICs exhibited an activated phenotype ex vivo, reminiscent of the activated pathogenic phenotype of Tg197-derived SFs. Significant functional similarities between SFs and VICs were revealed by RNA-seq analysis, demonstrating common cellular mechanisms underlying TNF-mediated arthritides and cardiac comorbidities.ConclusionsComorbidheart valve disease and chronic polyarthritis are efficiently modelled in the Tg197 arthritis model and share common TNF/TNFR1-mediated, mesenchymal cell-specific aetiopathogenic mechanisms.

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Section: Resultsmentioning

confidence: 99%

Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis

et al. 2018

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“…This suggests that not only inflammatory, but other aspects of immune functions might also have important roles during the development of atherosclerosis and CAD. The fact that certain autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus have been associated with higher prevalence of atherosclerosis, hypertension, and increased cardiovascular mortality, supports this statement (16,17). More detailed understanding of these mechanisms might help the identification of new biomarkers and potential therapeutic targets which may support both the follow-up and treatment of patients with cardiovascular diseases.…”

Section: Cad Atherosclerosis and Inflammationmentioning

confidence: 96%

Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease

et al. 2022

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Coronary artery disease (CAD) is one of the leading cause of mortality worldwide. Several risk factors including unhealthy lifestyle, genetic background, obesity, diabetes, hypercholesterolemia, hypertension, smoking, age, etc. contribute to the development of coronary atherosclerosis and subsequent coronary artery disease. Inflammation plays an important role in coronary artery disease development and progression. Pro-inflammatory signals promote the degradation of tryptophan via the kynurenine pathway resulting in the formation of several immunomodulatory metabolites. An unbalanced kynurenic pathway has been implicated in the pathomechanisms of various diseases including CAD. Significant improvements in detection methods in the last decades may allow simultaneous measurement of multiple metabolites of the kynurenine pathway and such a thorough analysis of the kynurenine pathway may be a valuable tool for risk stratification and determination of CAD prognosis. Nevertheless, imbalance in the activities of different branches of the kynurenine pathway may require careful interpretation. In this review, we aim to summarize clinical evidence supporting a possible use of kynurenine pathway metabolites as clinical biomarkers in various manifestations of CAD.

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“…A large number of RA patients have been found to have diastolic cardiac dysfunction prior to the established diagnosis of RA or with low disease activity (Targońska‐Stępniak et al., 2019). Accumulating clinical research and meta‐analysis have pointed out the critical role of pro‐inflammatory cytokines, metabolic disorders, excessive adrenergic stress and application of anti‐rheumatic drugs in the development of RA‐related CVD (Corrao et al., 2013; El Bakry et al., 2017). However, the mechanism underlying the pathogenic progress of developing cardiac dysfunction has not been clarified and experimental studies are still lacking.…”

Section: Discussionmentioning

confidence: 99%

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

Wang

Zhou

Guo

et al. 2021

Experimental Physiology

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Cardiovascular mortality has been increasing, and in particular, cardiovascular damage caused by some chronic autoimmune diseases accounts for a large proportion of this. C57BL/6J mice have been used mostly in studies of cardiovascular diseases. However, for purposes of modelling, this strain of mouse has a very low incidence of some chronic immune diseases such as rheumatoid arthritis, to which instead DBA/1 mice are more susceptible. Basic cardiac function differs between mice with different genetic backgrounds. Therefore, we monitored cardiac function and structure of normal male C57BL/6J and DBA/1 mice for six consecutive months. Echocardiography was used to monitor cardiac functions once a month and cardiac systolic function was measured upon isoproterenol challenge at the end of observation. The Excitationcontraction coupling-related proteins were measured by western blotting. Heart tissue sections were subject to haematoxylin-eosin, TUNEL and Alizarin red staining. The results demonstrated that systolic and diastolic function did not vary significantly and both strains were indistinguishable in appearance and structure of hearts. DBA/1 mice showed a good cardiac β-adrenergic response comparable to C57BL/6J mice with isoproterenol treatment. The phosphorylation of phospholamban at either its protein kinase A or its Ca 2+ /calmodulin-dependent protein kinase II site, as well as the activation of troponin I showed no significant difference between strains. These findings suggested that there was no obvious difference in the heart structure and function of normal male DBA/1 mice compared with C57BL/6J mice. The DBA/1 mouse is a strain applicable to investigating autoimmune disease-induced heart dysfunction and exploring potential interventions.

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Ischemic heart disease and rheumatoid arthritis: Do inflammatory cytokines have a role?

Cited by 12 publications

References 34 publications

Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis

Comorbid TNF-mediated heart valve disease and chronic polyarthritis share common mesenchymal cell-mediated aetiopathogenesis

Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease

DBA/1 mice display equivalent cardiac function to C57BL/6J mice

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