Inflammatory Cytokines, Immune Cells, and Organ Interactions in Heart Failure.
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ABSTRACT:
SUBMITTER: Li H
PROVIDER: S-EPMC8281681 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDistinct monocyte subsets predict cardiovascular risk and contribute to heart failure progression in murine models, but they have not been examined in clinical acute decompensated heart failure (ADHF).Methods and resultsBlood samples were obtained from 11 healthy control subjects (HCs) and at admission and discharge from 19 ADHF patients. Serologic markers of inflammation were assessed at admission and discharge. Monocyte populations were defined with the use of flow cytometry for cell-surface expression of CD14 and CD16: CD14++CD16- (classic), CD14++CD16+ (intermediate), and CD14+CD16++ (nonclassic). In ADHF patients, C-reactive protein (CRP) and interleukin-6 (IL-6) were higher compared with HCs (both P < .001) and decreased from admission to discharge (CRP: 12.1 ± 10.1 to 8.6 ± 8.4 mg/L [P = .005]; IL-6: 19.8 ± 34.5 to 7.1 ± 4.7 pg/mL [P = .08]). In ADHF patients, the admission proportion of CD14++CD16- monocytes was lower (68% vs 85%; P < .001) and that of CD14++CD16+ (15% vs 8%; P = .002) and CD14+CD16++ (17% vs 7%, P = .07) monocytes higher compared with HCs. Additionally, the proportion of CD14++CD16- monocytes increased (68% to 79%, P = .04) and the CD14+CD16++ monocytes decreased (17% to 7%, P = .049) between admission and discharge.ConclusionsFollowing standard treatment of ADHF, the monocyte profile and circulating inflammatory markers shifts to more closely resemble those of HC, suggesting a resolution of the acute inflammatory state. Functional studies are warranted to understand how specific monocyte subsets and systemic inflammation may contribute to ADHF pathophysiology.
| S-EPMC4861694 | biostudies-literature
Project description:Patients with chronic inflammatory diseases are at increased risk for heart failure due to ischemic heart disease and other causes including heart failure with preserved ejection fraction. Using rheumatoid arthritis and treated HIV infection as two prototypical examples, we review the epidemiology and potential therapies to prevent heart failure in these populations. Particular focus is given to anti-inflammatory therapies including statins and biologic disease modifying drugs. There is also limited evidence for lifestyle changes and blockade of the renin-angiotensin-aldosterone system. We conclude by proposing how a strategy for heart failure prevention, such as the model tested in the Screening To Prevent Heart Failure (STOP-HF) trial, may be adapted to chronic inflammatory disease.
| S-EPMC4548924 | biostudies-literature
Project description:Heart failure-either with reduced or preserved ejection fraction (HFrEF/HFpEF)-is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body's needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.
| S-EPMC8562335 | biostudies-literature
Project description:Betel nut consumption has significant implications for the public health globally, as the wide-spread habit of Areca chewing throughout Asia and the Pacific is associated with a high prevalence of oral carcinoma and other diseases. Despite a clear causal association of betel nut chewing and oral mucosal diseases, the biological mechanisms that link Areca nut-contained molecules, inflammation and cancer remain underexplored. In this study we show that the whole Areca nut extract (ANE) is capable of mobilizing Ca2+ in various immune cell lines. Interestingly, none of the four major alkaloids or a range of other known constituents of Areca nut were able to induce such Ca2+ signals, suggesting that the active components might represent novel or so far unappreciated chemical structures. The separation of ANE into aqueous and organic fractions has further revealed that the calcium-mobilizing molecules are exclusively present in the aqueous extract. In addition, we found that these calcium signals are associated with the activation of several immune cell lines as shown by the release of pro-inflammatory cytokines and increased cell proliferation. These results indicate that calcium-mobilizing molecules present in the aqueous fraction of the Areca nut may critically contribute to the inflammatory disorders affecting betel nut chewers.
| S-EPMC5773534 | biostudies-literature
Project description:Heart failure (HF) is accompanied by the upregulation of bioactive signaling molecules, known as cytokines, and a family of downstream proteases, matrix metalloproteinases (MMPs). It is now apparent that these molecules contribute to adverse myocardial remodeling during HF. Elevated levels of cytokines and MMPs exist in the myocardium and can subsequently spill over into the systemic circulation. The purpose of this article is to examine clinical studies of HF that have quantified levels of different types of cytokines, MMPs and endogenous tissue inhibitors of MMPs in relation to this disease process. HF is a complex syndrome that can develop from various etiologies and can be characterized into two distinct phenotypes: systolic and diastolic. This article will present recent clinical studies that have identified significant differences between the cytokine and MMP circulating profile of systolic and diastolic HF patients. In general, elevated levels of cytokines and MMPs exist in systolic HF patients when compared with diastolic HF patients, whereas diastolic HF patients have elevated levels of cytokines and MMPs when compared with controls. Therefore, future studies distinguishing between HF phenotypes may provide more consistent results in determining possible analytes to be used as biomarkers. Furthermore, this article will emphasize why standardization of analytical techniques and establishment of referent cytokine and MMP levels are necessary if these analytes are to be used as biomarkers for the diagnosis, prognosis and evaluation of treatment in the context of HF.
| S-EPMC2794436 | biostudies-literature
Project description:Complete and accurate DNA replication is essential to genome stability maintenance during cellular division. However, cells are routinely challenged by endogenous as well as exogenous agents that threaten DNA stability. DNA breaks and the activation of the DNA damage response (DDR) arising from endogenous replication stress have been observed at pre- or early stages of oncogenesis and senescence. Proper detection and signalling of DNA damage are essential for the autonomous cellular response in which the DDR regulates cell cycle progression and controls the repair machinery. In addition to this autonomous cellular response, replicative stress changes the cellular microenvironment, activating the innate immune response that enables the organism to protect itself against the proliferation of damaged cells. Thereby, the recent descriptions of the mechanisms of the pro-inflammatory response activation after replication stress, DNA damage and DDR defects constitute important conceptual novelties. Here, we review the links of replication, DNA damage and DDR defects to innate immunity activation by pro-inflammatory paracrine effects, highlighting the implications for human syndromes and immunotherapies.
| S-EPMC7230342 | biostudies-literature
Project description:AimsThere are limited data examining the role of immune checkpoint (IC) ligands in the pathophysiology of heart failure (HF). Therefore, we explore this in three HF animal models and in three different human cohorts (healthy, stable, and worsening HF).Methods and resultsTranscriptomic analyses of cardiac tissue of three different HF mouse models revealed differentially expressed IC receptors and their ligands compared with control mice. Based on this observation, serum levels of three well-known IC ligands (i.e. sPD-L1, sPD-L2 and galectin-9) were measured in stable HF patients from the Vitamin D Chronic Heart Failure (VitD-CHF) study (n = 101), as well as healthy individuals from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study (n = 58). sPD-L1, sPD-L2, and galectin-9 were all associated with New York Heart Association classification. In multivariate linear regression analyses, all three IC ligands were associated with galectin-3 (β = 0.230, β = 0.283, and β = 0.304, respectively). sPD-L1 and galectin-9 were also associated with hs-troponin-T (β = 0.386 and β = 0.314). Regarding prognosis, higher serum levels of sPD-L1 and galectin-9 were significantly associated with increased risk for HF hospitalization and all-cause mortality [hazard ratio 1.69 (1.09-2.59) and hazard ratio 1.50 (1.06-2.12)]. Furthermore, the importance of IC ligands was tested in another stage of HF, namely worsening HF patients. In the worsening HF cohort (The BIOlogy Study to Tailored Treatment in Chronic Heart Failure) (n = 2032), sPD-L2 and galectin-9 were associated with New York Heart Association classification and significantly predicted outcome with an increased relative risk of 15% and 20%, after multivariable adjustment, respectively.ConclusionsIC ligands are expressed in cardiac disease models, and serum levels of IC ligands are elevated in HF patients, are associated with disease severity, and significantly predict prognosis. These data indicate a potential role for IC ligands in HF pathogenesis.
| S-EPMC10375122 | biostudies-literature
Project description:Inflammation is a well-known feature of heart failure. Studies have shown that while some inflammation is required for repair during injury and is protective, prolonged inflammation leads to myocardial remodeling and apoptosis of cardiac myocytes. Various types of immune cells are implicated in myocardial inflammation and include neutrophils, macrophages, eosinophils, mast cells, natural killer cells, T cells, and B cells. Recent clinical trials have targeted inflammatory cascades as therapy for heart failure with limited success. A better understanding of the temporal course of the infiltration of the different immune cells and their contribution to the inflammatory process may improve the success for therapy. This brief review outlines the major cell types involved in heart failure, and some of their actions are summarized in the supplementary figure.
| S-EPMC6745095 | biostudies-literature
Project description:BackgroundSepsis, a life-threatening organ dysfunction caused by a dysregulated systemic immune response to infection, associates with reduced responsiveness to subsequent infections. How such tolerance is acquired is not well understood but is known to involve epigenetic and transcriptional dysregulation.MethodsBead arrays were used to compare global DNA methylation changes in patients with sepsis, non-infectious systemic inflammatory response syndrome, and healthy controls. Bioinformatic analyses were performed to dissect functional reprogramming and signaling pathways related to the acquisition of these specific DNA methylation alterations. Finally, in vitro experiments using human monocytes were performed to test the induction of similar DNA methylation reprogramming.ResultsHere, we focused on DNA methylation changes associated with sepsis, given their potential role in stabilizing altered phenotypes. Tolerized monocytes from patients with sepsis display changes in their DNA methylomes with respect to those from healthy controls, affecting critical monocyte-related genes. DNA methylation profiles correlate with IL-10 and IL-6 levels, significantly increased in monocytes in sepsis, as well as with the Sequential Organ Failure Assessment score; the observed changes associate with TFs and pathways downstream to toll-like receptors and inflammatory cytokines. In fact, in vitro stimulation of toll-like receptors in monocytes results in similar gains and losses of methylation together with the acquisition of tolerance.ConclusionWe have identified a DNA methylation signature associated with sepsis that is downstream to the response of monocytes to inflammatory signals associated with the acquisition of a tolerized phenotype and organic dysfunction.
| S-EPMC6820973 | biostudies-literature
Project description:INTRODUCTION/PURPOSE:Inflammation contributes to heart failure (HF) progression and the interleukin (IL)-1 cytokine IL-1? is implicated in this process. The adaptor protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is necessary for inflammasome activation of IL-1?. Lower ASC methylation is associated with worse outcomes in HF. The purpose of this study was to examine the effects of exercise on changes in ASC methylation and activation of the IL-1 family cytokine IL-1? in persons with HF. METHODS:Participants (N = 54) were randomized to receive exercise intervention (n = 38) or attention control (n = 16) for 3 months. Percent methylation of the ASC gene, plasma IL-1?, and ASC mRNA and were obtained at baseline, 3 months, and 6 months. RESULTS:ASC methylation was higher in the exercise group as compared to control at 3 months (6.10% ± 0.5% vs 5.80% ± 0.4%; P = 0.04) and 6 months (6.07 ± 0.4 vs 5.82 ± 0.4; P = 0.04). Plasma IL-1? was lower in the exercise group at 3 months (1.43 ± 0.5 pg·mL vs 2.09 ± 1.3 pg·mL; P = 0.02) and 6 months (1.49 ± 0.5 pg·mL vs 2.13 ± 1.4 pg·mL; P = 0.004). ASC mRNA expression was negatively associated with ASC methylation at baseline (r = -0.97, P = 0.001), 3 months (r = -0.90, P = 0.001), and 6 months (r = -0.81, P = 0.001). ASC mRNA was lower than baseline at 3 months (P = 0.004) and 6 months (P = 0.002) among those in the exercise group. ASC methylation was positively associated with 6-min walk test at baseline (r = 0.517, P < 0.001), 3 months (r = 0.464, P = 0.004), and 6 months (r = 497, P = 0.05). CONCLUSIONS:Exercise was related to increased mean percent ASC methylation and decreased IL-1? and ASC mRNA gene expression in HF. Epigenetic regulation of ASC can be a biological mechanism by which exercise can promote better outcomes in HF.
| S-EPMC6095733 | biostudies-literature