Cardiac cytokine therapy? Relevance of targeting inflammatory mediators to combat cardiac arrhythmogenic remodeling

Hiram, Roddy

doi:10.1016/j.ijcha.2021.100918

Cited by 5 publications

(4 citation statements)

References 20 publications

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“…Our current study suggests that novel therapeutic approaches may include inflammation-resolution strategies to prevent or cure the inflammatory status, which is commonly observed in AF and RHD. 2 , 38 , 52–55 In addition, SERCA2a is also dysregulated in both PAH and AF, 56 , 57 suggesting that strategies promoting the normal expression and activity of SERCA2a may contribute to preventing AF occurrence in RHD-induced arrhythmogenicity. In a rabbit model of left heart failure, upregulation of SERCA2a was associated with LA cardio-protection and reduction of atrial vulnerability to arrhythmogenicity.…”

Section: Discussionmentioning

confidence: 99%

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Le Quilliec,

LeBlanc,

Neuilly

et al. 2024

Europace

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Context Right heart disease (RHD), characterized by right ventricular (RV) and atrial (RA) hypertrophy, and cardiomyocytes’ (CM) dysfunctions have been described to be associated with the incidence of atrial fibrillation (AF). RHD and AF have in common, an inflammatory status, but the mechanisms relating RHD, inflammation, and AF remain unclear. Hypotheses RHD generates electrophysiological and morphological remodelling affecting the CM, leading to atrial inflammation and increased AF susceptibility. Methods Pulmonary artery banding (PAB) was surgically performed (except for sham) on male Wistar rats (225-275g) to provoke an RHD. Twenty-one days (D21) post-surgery, all rats underwent echocardiography and electrophysiological studies (EPS). Optical mapping was performed in situ, on Langendorff-perfused hearts. The contractility of freshly isolated CM was evaluated and recorded during 1 Hz pacing in vitro. Histological analyses were performed on formalin-fixed RA to assess myocardial fibrosis, Connexin-43 (Cx43) levels, and CM morphology. RA levels of selected genes and proteins were obtained by qPCR and Western-blot respectively. Results PAB induced severe RHD identified by RV and RA hypertrophy. PAB rats were significantly more susceptible to AF than sham. Compared to sham RA CM from PAB rats were significantly elongated, and hypercontractile. RA CM from PAB animals showed significant augmentation of mRNA and protein levels of proinflammatory interleukin (IL)-6 and IL1β. Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) and junctophilin-2 (JPH2) were decreased in RA CM from PAB compared to sham rats. Conclusions RHD-induced arrhythmogenicity may occur due to dysfunctional SERCA2a and inflammatory signalling generated from injured RA CM, which leads to an increased risk of AF.

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Section: Discussionmentioning

confidence: 99%

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Le Quilliec,

LeBlanc,

Neuilly

et al. 2024

Europace

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“…The NLRP3 inflammasome is implicated in the development and progression of multiple cardiovascular maladies such as systemic hypertension, myocardial infarction, or cardiac arrhythmias [ 114 ]. The assembled and activated NLRP3 inflammasome promotes the maturation of the inactive isoforms pro-interleukin-(IL)-1β and pro-IL-18 into active IL-1β and IL-18 [ 109 , 113 , 114 , 115 ]. Moreover, NLRP3-induced gasdermin-D (GSDMD) cleavage into N-terminus GSDMD (GSDMD-Nt) generates the formation of pores through the cellular membrane allowing the products of the inflammasome activity, including IL-1β and IL-18 to be excreted and play further autocrine, paracrine, and endocrine pro-inflammatory signaling [ 116 ].…”

Section: Proposed Mechanisms Underlying the Association Between Pesti...mentioning

confidence: 99%

Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review

Le Quilliec,

Fundere,

Al-U’datt

et al. 2023

Biomedicines

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Atrial fibrillation (AF) is the most common type of cardiac rhythm disorder. Recent clinical and experimental studies reveal that environmental pollutants, including organophosphorus–organochloride pesticides and air pollution, may contribute to the development of cardiac arrhythmias including AF. Here, we discussed the unifying cascade of events that may explain the role of pollutant exposure in the development of AF. Following ingestion and inhalation of pollution-promoting toxic compounds, damage-associated molecular pattern (DAMP) stimuli activate the inflammatory response and oxidative stress that may negatively affect the respiratory, cognitive, digestive, and cardiac systems. Although the detailed mechanisms underlying the association between pollutant exposure and the incidence of AF are not completely elucidated, some clinical reports and fundamental research data support the idea that pollutant poisoning can provoke perturbed ion channel function, myocardial electrical abnormalities, decreased action potential duration, slowed conduction, contractile dysfunction, cardiac fibrosis, and arrhythmias including AF.

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“…Various chronic cardiac inflammatory diseases, including AF, have in common the overexpression of NLRP3 inflammasome-related genes and components [88][89][90][91][92]. The NLRP3 inflammasome senses PAMPs and DAMPs signals to promote proinflammatory response to infection or injury by stimulating secretion of proinflammatory interleukins such as IL1β, IL6, and IL18 [93,94]. Genetic deficiency of NLRP3 was associated with reduced expression of proinflammatory cytokines (TNFα, IL1β, IL6), reduced secretion of proinflammatory PGE 2 and LTB 4 , and increased expression of LXA 4 and LXB 4 , which suggests that presence of NLRP3 may negatively influence the LM-class switching and prevent resolution process during acute inflammation [95].…”

Section: Nlrp3-inflammasome Il1 and Il6 Inhibitionmentioning

confidence: 99%

Resolution-promoting autacoids demonstrate promising cardioprotective effects against heart diseases

Hiram

2022

Mol Biol Rep

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Chronic heart diseases have in common an unresolved inflammatory status. In atherosclerosis, myocarditis, myocardial infarction, or atrial fibrillation, mounting evidence suggests that unresolved inflammation contributes to the chronicity, aggravation, and morbidity of the disease. Following cardiac injury or infection, acute inflammation is a normal and required process to repair damaged tissues or eliminate pathogens and promote restoration of normal functions and structures. However, if acute inflammation is not followed by resolution, a chronic and deleterious inflammatory status may occur, characterized by the persistence of inflammatory biomarkers, promoting aggravation of myocardial pathogenesis, abnormal structural remodeling, development of cardiac fibrosis, and loss of function. Although traditional antiinflammatory strategies, including the use of COX-inhibitors, to inhibit the production of inflammation promotors failed to promote homeostasis, mounting evidence suggests that activation of specific endogenous autacoids may promote resolution and perpetuate cardioprotective effects. The recent discovery of the active mechanism of resolution suggests that proresolving signals and cellular processes may help to terminate inflammation and combat the development of its chronic profile in cardiac diseases. This review discussed (I) the preclinical and clinical evidence of inflammation-resolution in cardiac disorders including atrial fibrillation; (II) how and why many traditional antiinflammatory treatments failed to prevent or cure cardiac inflammation and fibrosis; and (III) whether new therapeutic strategies may interact with the resolution machinery to have cardioprotective effects. Graphical abstract RvD D-series resolving, RvE E-series resolving, LXA4 lipoxin A4, MaR1 maresin-1

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Cardiac cytokine therapy? Relevance of targeting inflammatory mediators to combat cardiac arrhythmogenic remodeling

Cited by 5 publications

References 20 publications

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Atrial cardiomyocytes contribute to the inflammatory status associated with atrial fibrillation in right heart disease

Pollutants, including Organophosphorus and Organochloride Pesticides, May Increase the Risk of Cardiac Remodeling and Atrial Fibrillation: A Narrative Review

Resolution-promoting autacoids demonstrate promising cardioprotective effects against heart diseases

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