Proinflammatory Cytokine Activation Is Linked to Apoptotic Mediator, Soluble Fas Level in Patients With Chronic Heart Failure

Kinugawa, Toru; Kato, Masahiko; Yamamoto, Kazuhide; Hisatome, Ichiro; Nohara, Ryuji

doi:10.1536/ihj.53.182

Cited by 24 publications

(22 citation statements)

References 35 publications

(37 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…High levels of accumulated pro-inflammatory factors induce various pathogenic effects, such as improper functioning of the left ventricle, cardiomyocyte death and/or fibrosis [8-10]. It was shown that inflammatory mediators, such as IL-6 and tumor necrosis factor - alpha (TNF-α) can activate apoptotic Fas-Fas ligand pathway in chronic heart failure [11]. Additionally, inflammatory cytokines activate members of the matrix metalloproteinase (MMP) family, zinc-depended endopeptidases, which participate in remodeling of ECM and fibrotic processes [12].…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Bironaitė

Daunoravičius

Bogomolovas

et al. 2015

BMC Cardiovasc Disord

View full text Add to dashboard Cite

BackgroundInflammatory dilated cardiomyopathy (iDCM) is a common debilitating disease with poor prognosis that often leads to heart failure and may require heart transplantation. The aim of this study was to evaluate sera and biopsy samples from chronic iDCM patients, and to investigate molecular mechanism associated with left ventricular remodeling and disease progression in order to improve therapeutic intervention.MethodsPatients were divided into inflammatory and non-inflammatory DCM groups according to the immunohistochemical expression of inflammatory infiltrates markers: T-lymphocytes (CD3), active-memory T lymphocyte (CD45Ro) and macrophages (CD68). The inflammation, apoptosis, necrosis and fibrosis were investigated by ELISA, chemiluminescent, immunohistochemical and histological assays.ResultsThe pro-inflammatory cytokine IL-6 was significantly elevated in iDCM sera (3.3 vs. 10.98 μg/ml; P < 0.05). Sera levels of caspase-9, −8 and −3 had increased 6.24-, 3.1- and 3.62-fold, (P < 0.05) and only slightly (1.3-, 1.22- and 1.03-fold) in biopsies. Significant release of Hsp60 in sera (0.0419 vs. 0.36 ng/mg protein; P < 0.05) suggested a mechanistic involvement of mitochondria in cardiomyocyte apoptosis. The significant MMP9/TIMP1 upregulation in biopsies (0.1931 - 0.476, P < 0.05) and correlation with apoptosis markers show its involvement in initiation of cell death and ECM degradation. A slight activation of the extrinsic apoptotic pathway and the release of hsTnT might support the progression of chronic iDCM.ConclusionsData of this study show that significant increase of IL-6, MMP9/TIMP1 and caspases-9, −8, −3 in sera corresponds to molecular mechanisms dominating in chronic iDCM myocardium. The initial apoptotic pathway was more activated by the intramyocardial inflammation and might be associated with extrinsic apoptotic pathway through the pro-apoptotic Bax. The activated intrinsic form of myocardial apoptosis, absence of necrosis and decreased fibrosis are most typical characteristics of chronic iDCM. Clinical use of anti-inflammatory drugs together with specific anti-apoptotic treatment might improve the efficiency of therapies against chronic iDCM before heart failure occurs.

show abstract

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Bironaitė

Daunoravičius

Bogomolovas

et al. 2015

BMC Cardiovasc Disord

View full text Add to dashboard Cite

show abstract

“…As a complex clinical syndrome, CHF activates the immune system and inflammatory responses and is thus characterized by elevated levels of proinflammatory cytokines in the circulation. [2][3][4] Therefore, various inflammatory markers have become a major focus of interest in CHF research. 5,6) The neutrophil-to-lymphocyte (N/L) ratio is an emerging composite inflammatory marker.…”

mentioning

confidence: 99%

Usefulness of the Neutrophil-to-Lymphocyte Ratio in Predicting Adverse Events in Elderly Patients With Chronic Heart Failure

Yan

et al. 2016

Int. Heart J.

View full text Add to dashboard Cite

SummaryThe neutrophil-to-lymphocyte (N/L) ratio has been associated with poor outcomes in patients with cardiovascular diseases, but it has not been studied in elderly patients with chronic heart failure (CHF).In this study, we analyzed 1355 elderly patients admitted with CHF. A multivariate logistic regression model was used to assess the independent association of the N/L ratio with chronic kidney disease (CKD). The patients were then divided into tertiles according to the N/L ratios. We used Cox regression analysis to assess the association between the N/L ratio and subsequent major cardiovascular events (MCE), including cardiac death and rehospitalization for heart failure.In the multiple logistic regression analysis, the N/L ratio was identified as a risk factor for CKD in elderly patients with CHF (odds ratio [OR] = 1.170, 95% confidence interval [CI] 1.054 to 1.298, P = 0.003). The median follow-up period was 18 months. In a multivariate analysis with the lowest tertile as the reference, the highest tertile of the N/L ratio remained significantly associated with MCE (hazard ratio [HR] = 1.425, 95% CI 1.109 to 1.832, P = 0.006), cardiac death (HR = 1.747, 95% CI 1.032 to 2.958, P = 0.038), and rehospitalization for heart failure (HR = 1.461, 95% CI 1.108 to 1.927, P = 0.007).In elderly patients with CHF, the N/L ratio is one of the important risk factors for CKD and the highest tertile of the N/L ratio is associated with an increased risk for MCE. (Int Heart J 2016; 57: 615-621)

show abstract

“…However, variable differences in these biomarkers existed between patients with HFrEF and those of group 3. IL-6, involved in a major apoptosis signaling pathway that is upregulated in chronic HF, 20 differed across groups: with group 1 having the highest values and group 2 having intermediate values. Levels of IL-10, which suppresses the production of TNF-α and other proinflammatory cytokines and counteracts many of the adverse effects of TNF-α on cardiac function, 21 were higher in group 1 when compared with those in group 2 but were comparable between groups 1 and 3.…”

Section: Discussionmentioning

confidence: 99%

Heart Failure With Anemia

O’Meara

Rouleau

White

et al. 2014

Circ: Heart Failure

View full text Add to dashboard Cite

Background— Anemia is a highly prevalent and strong independent prognostic marker in heart failure (HF), yet this association is not completely understood. Whether anemia is simply a marker of disease severity and concomitant chronic kidney disease or represents the activation of other detrimental pathways remains uncertain. We sought to determine which pathophysiological pathways are exacerbated in patients with HF, reduced ejection fraction (HFrEF) and anemia in comparison with those without anemia. Methods and Results— In a prospective study involving 151 patients, selected biomarkers were analyzed, each representing proposed contributive mechanisms in the pathophysiology of anemia in HF. We compared clinical, echocardiographic, and circulating biomarkers profiles among patients with HFrEF and anemia (group 1), HFrEF without anemia (group 2), and chronic kidney disease with preserved EF, without established HF (chronic kidney disease control group 3). We demonstrate here that many processes other than those related to chronic kidney disease are involved in the anemia–HF relationship. These are linked to the pathophysiological mechanisms pertaining to left ventricular systolic dysfunction and remodeling, systemic inflammation and volume overload. We found that levels of interleukin-6 and interleukin-10, specific markers of cardiac remodeling (procollagen type III N-terminal peptide, matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase 1, left atrial volume), myocardial stretch (NT-proBNP [N-terminal probrain natriuretic peptide]), and myocyte death (troponin T) are related to anemia in HFrEF. Conclusions— Anemia is strongly associated not only with markers of more advanced and active heart disease but also with the level of renal dysfunction in HFrEF. Increased myocardial remodeling, inflammation, and volume overload are the hallmarks of patients with anemia and HF. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00834691.

show abstract

Proinflammatory Cytokine Activation Is Linked to Apoptotic Mediator, Soluble Fas Level in Patients With Chronic Heart Failure

Cited by 24 publications

References 35 publications

Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Molecular mechanisms behind progressing chronic inflammatory dilated cardiomyopathy

Usefulness of the Neutrophil-to-Lymphocyte Ratio in Predicting Adverse Events in Elderly Patients With Chronic Heart Failure

Heart Failure With Anemia

Contact Info

Product

Resources

About