Etanercept protects rat cardiomyocytes against hypertrophy by regulating inflammatory cytokines secretion and cell apoptosis

Li, Q; Yu, Qinggong; Na, R; Liu, B

doi:10.1590/1414-431x20175868

Cited by 5 publications

(6 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effects of these drugs on myocardial remodeling and diastolic dysfunction have been contradictory (Kosmas et al, 2019). Some have shown that blocking circulating inflammatory cytokines positively impacts the cellular mechanisms implicated in myocardial remodeling (Kleveland et al, 2016; Li et al, 2017), while others have failed to show positive outcomes (Hartman et al, 2016). Nevertheless, the beneficial effects were shown in systems that did not involve chronic inflammation (Kleveland et al, 2016; Li et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…Some have shown that blocking circulating inflammatory cytokines positively impacts the cellular mechanisms implicated in myocardial remodeling (Kleveland et al, 2016; Li et al, 2017), while others have failed to show positive outcomes (Hartman et al, 2016). Nevertheless, the beneficial effects were shown in systems that did not involve chronic inflammation (Kleveland et al, 2016; Li et al, 2017). We have recently shown that systemic inflammation‐induced concentric remodeling, diastolic dysfunction (Le Roux et al, 2021; Mokotedi et al, 2020), and increased collagen area fraction (Mokotedi et al, 2020) in the collagen‐induced arthritis (CIA) rat model.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inflammation‐induced left ventricular fibrosis is partially mediated by tumor necrosis factor‐α

Manilall

Mokotedi

Gunter

et al. 2021

Physiological Reports

View full text Add to dashboard Cite

Objective To determine the mechanisms of inflammation‐induced left ventricular (LV) remodeling and effects of blocking circulating tumor necrosis factor alpha (TNF‐α) in a model of systemic inflammation. Methods Seventy Sprague‐Dawley rats were divided into three groups: the control group, the collagen‐induced arthritis (CIA) group, and the anti‐TNF‐α group. Inflammation was induced in the CIA and anti‐TNF‐α groups. Following the onset of arthritis, the anti‐TNF‐α group received the TNF‐α inhibitor, etanercept, for 6 weeks. LV geometry and function were assessed with echocardiography. Circulating inflammatory markers were measured by ELISA and LV gene expression was assessed by comparative TaqMan® polymerase chain reaction. Results The LV relative gene expression of pro‐fibrotic genes, transforming growth factor β (TGFβ) (p = 0.03), collagen I (Col1) (p < 0.0001), and lysyl oxidase (LOX) (p = 0.002), was increased in the CIA group compared with controls, consistent with increased relative wall thickness (p = 0.0009). Col1 and LOX expression in the anti‐TNF‐α group were similar to controls (both, p > 0.05) and tended to be lower compared to the CIA group (p = 0.06 and p = 0.08, respectively), and may, in part, contribute to the decreased relative wall thickness in the anti‐TNF‐α group compared to the CIA group (p = 0.03). In the CIA group, the relative gene expression of matrix metalloproteinase 2 (MMP2) and MMP9 was increased compared to control (p = 0.04) and anti‐TNF‐α (p < 0.0001) groups, respectively. Conclusion Chronic systemic inflammation induces fibrosis and dysregulated LV extracellular matrix remodeling by increasing local cardiac pro‐fibrotic gene expression, which is partially mediated by TNF‐α. Inflammation‐induced LV diastolic dysfunction is likely independent of myocardial fibrosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Inflammation‐induced left ventricular fibrosis is partially mediated by tumor necrosis factor‐α

Manilall

Mokotedi

Gunter

et al. 2021

Physiological Reports

View full text Add to dashboard Cite

show abstract

“…In human cardiac tissues under ischemic injury local production of TNF coupled with hypoxia-mediated induction of TNFR2 facilitate the transient proliferation and eventually differentiation of resident cardiac stem cells into mature cardiac myocytes [ 106 ]. Contrary to this in various models of experimental cardiac hypertrophy, TNF inhibitor was able to reduce heart hypertrophy, which was believed to be mediated by a reduction of levels of myocardial hypertrophy marker genes, including atrial natriuretic factor (ANF), matrix metalloproteinase (MMP)-9, and MMP-13 [ 107 ]. It is plausible that in these models TNF inhibitors blocks TNF signaling mediated by TNFR1 [ 108 ].…”

Section: The Role Of Tnf In Rheumatoid Arthritis and Heart Failurementioning

confidence: 99%

Bimodal Function of Anti-TNF Treatment: Shall We Be Concerned about Anti-TNF Treatment in Patients with Rheumatoid Arthritis and Heart Failure?

Kotyla

2018

IJMS

View full text Add to dashboard Cite

Treatment with anti-TNF-α (tumor necrosis factor), one of the pivotal cytokines, was introduced to clinical practice at the end of last century and revolutionized the treatment of rheumatoid arthritis (RA) as well as many other inflammatory conditions. Such a treatment may however bring many safety issues regarding infections, tuberculosis, as well as cardiovascular diseases, including heart failure. Given the central role of proinflammatory cytokines in RA, atherosclerosis, and congestive heart failure (CHF), such a treatment might result in better control of the RA process on the one side and improvement of heart function on the other. Unfortunately, at the beginning of this century two randomized controlled trials failed to show any benefit of anti-TNF treatment in patients with heart failure (HF), suggesting direct negative impact of the treatment on morbidity and mortality in HF patients. As a result the anti-TNF treatment is contraindicated in all patients with heart failure and a substantial portion of patients with RA and impaired heart function are not able to benefit from the treatment. The role of TNF in CHF and RA differs substantially with regard to the source and pathophysiological function of the cytokine in both conditions, therefore negative data from CHF studies should be interpreted with caution. At least some of RA patients with heart failure may benefit from anti-TNF treatment, as it results not only in the reduction of inflammation but also contributes significantly to the improvement of cardiac function. The paper addresses the epidemiological data of safety of anti-TNF treatment in RA patients with the special emphasis to basic pathophysiological mechanisms via which TNF may act differently in both diseases.

show abstract

“…A liver X receptor agonist (TO901317) inhibits oxLDL-induced mitogenic effects of CT-1 [94]. Etanercept, a TNF-α inhibitor, decreases CT-1 levels secreted from neonatal rat cardiomyocytes [95]. These interventions against CT-1 may provide therapeutic advances for atherosclerotic cardiovascular diseases.…”

Section: Pharmacological Intervention Against Ct-1mentioning

confidence: 99%

Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

Watanabe

Konii

Sato

2018

View full text Add to dashboard Cite

Cardiotrophin-1 (CT-1), an interleukin-6 family cytokine, is known as an active inducer capable of cardiac hypertrophy and vascular stiffness in hypertensive heart disease. CT-1 is expressed at high levels in the heart, vascular endothelial cells (ECs), and adipocytes. CT-1 stimulates inflammatory and proatherogenic molecule expression in human monocytes and ECs, as well as monocyte-EC adhesion. CT-1 enhances oxidized low-density lipoprotein-induced foam-cell formation in human monocyte-derived macrophages. CT-1 stimulates the migration, proliferation, and colloagen-1 production in human vascular smooth muscle cells. Chronic CT-1 infusion into Apoe −/− mice accelerates the development of aortic atherosclerotic lesions. CT-1 is expressed at high levels in ECs and macrophage foam cells within atheromatous plaques in Apoe −/− mice. A blockade of CT-1 using anti-CT-1 neutralizing antibody results in the prevention of atherogenesis in Apoe −/− mice. Plasma CT-1 concentrations are elevated in patients with hypertensive heart disease, ischemic heart disease, and metabolic syndrome, and are positively associated with the severity of cardiac hypertrophy, heart failure, and atherosclerosis. Increased plasma concentration of CT-1 is a predictor of death and heart failure following acute myocardial infarction. Therefore, CT-1 serves a novel therapeutic target for atherosclerosis and related diseases. Plasma CT-1 may be a reliable biomarker for atherosclerotic cardiovascular diseases.J 2018, 1 95 have provided the first evidence that CT-1 is expressed at high levels in atherosclerotic lesions and shows proatherogenic effects [15]. Other studies have reported that plasma concentrations of CT-1 are increased in patients with coronary artery disease (CAD) [16].The present review introduces the recent accumulating evidence regarding the roles of CT-1 in the pathophysiology of atherosclerosis and the potential biomarker of cardiovascular and metabolic diseases. Structure, Expression, and Function of CT-1CT-1 is a new member of the interleukin (IL)-6 cytokine family that was originally cloned from a mouse embryoid body cDNA library based on its ability to induce hypertrophy in neonatal cardiomyocytes [17]. cDNA clones of human CT-1 were isolated by screening a heart cDNA library with a mouse CT-1 probe [17]. The DNA sequence of these clones encodes a protein of 201 amino acids that is 80% identical with the 203 amino acid residue of mouse CT-1 [18]. CT-1 has a molecular weight of 21.5 kDa. Human and mouse CT-1 lack a conventional, hydrophobic, N-terminal amino acid sequence indicative of a secretion signal [18]. The amino acid sequence of rat CT-1 is 80% and 94% identical to those of human CT-1 and mouse CT-1, respectively [19]. The coding region of CT-1 is contained on 3 exons and is located on human chromosome 16p11.1-16p11.2 [18].CT-1 is expressed in the cardiovascular system as well as the brain, thymus, lungs, kidneys, liver, intestine, testes, prostate, skeletal muscles, and adipose tissue [18][19][20][21][22][23]. In cardiov...

show abstract

Etanercept protects rat cardiomyocytes against hypertrophy by regulating inflammatory cytokines secretion and cell apoptosis

Cited by 5 publications

References 42 publications

Inflammation‐induced left ventricular fibrosis is partially mediated by tumor necrosis factor‐α

Inflammation‐induced left ventricular fibrosis is partially mediated by tumor necrosis factor‐α

Bimodal Function of Anti-TNF Treatment: Shall We Be Concerned about Anti-TNF Treatment in Patients with Rheumatoid Arthritis and Heart Failure?

Emerging Roles of Cardiotrophin-1 in the Pathogenesis and Biomarker of Atherosclerosis

Contact Info

Product

Resources

About