TWEAK/Fn14 Axis: A Promising Target for the Treatment of Cardiovascular Diseases

Blanco-Colio, Luís Miguel

doi:10.3389/fimmu.2014.00003

Cited by 67 publications

(82 citation statements)

References 126 publications

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“…In contrast to its substantial expression in injured and morbid tissues, Fn14 is rarely expressed in healthy tissues, which distinguishes it from TWEAK (26). Studies have indicated that Fn14 is expressed in the liver following partial hepatectomy and chemical injury (27,28), in the vasculature following balloon catheter injury (22), in the kidney after acute kidney injury and in the heart after myocardial infarction (29).…”

Section: The Role Of Tumor Necrosis Factor-like Weak Inducer Of Apoptmentioning

confidence: 99%

“…The association may provoke the activation of nuclear factor (NF)-κB. Notably, TWEAK, is able to induce prolonged NF-κB activation compared with TNF (26).…”

Section: The Role Of Tumor Necrosis Factor-like Weak Inducer Of Apoptmentioning

confidence: 99%

“…Assisted by MCP-1 and other chemokines, monocytes are recruited to endothelium and subsequently, due to high expression level of endothelial adhesion molecules (such as ICAM-1 and VCAM), monocytes continue to move into the subendothelial space to differentiate into macrophages (15,26). Following this, monocyte-derived macrophages, induced by ox-LDL, begin to proliferate and extend inflammatory responses (46), thereby increasing the secretion of proinflammatory cytokines, such as IL-6 and -8, and matrix metalloproteinases (MMPs), including MMP-9 (31).…”

Section: Inf Lammatory Response Of Monocytes/macrophagesmentioning

confidence: 99%

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The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors

Liu

Lin

Xiang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. At present, it is commonly accepted that atherosclerosis is a chronic inflammatory disease characterized by disorder of the arterial wall. As one of the inflammatory cytokines of the tumor necrosis factor superfamily, tumor necrosis factor-like weak inducer of apoptosis (TWEAK) participates in the formation and progression of atherosclerosis. TWEAK, when binding to its initial receptor, fibroblast growth factor inducible molecule 14 (Fn14), exerts adverse biological functions in atherosclerosis, including dysfunction of endothelial cells, phenotypic change of smooth muscle cells and inflammatory responses of monocytes/macrophages. However, accumulating data supports that, besides Fn14, TWEAK also binds to cluster of differentiation (CD)163, an anti-inflammatory cytokine and a scavenger receptor exclusively expressed by monocytes and macrophages. Furthermore, it has been demonstrated that CD163 is able to internalize TWEAK and likely elicits protective effects in atherosclerosis by terminating inflammation induced by TWEAK. In the present study, the role of TWEAK in atherosclerosis was reviewed, with a predominant focus on CD163 and Fn14 receptors.

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Section: The Role Of Tumor Necrosis Factor-like Weak Inducer Of Apoptmentioning

confidence: 99%

“…The association may provoke the activation of nuclear factor (NF)-κB. Notably, TWEAK, is able to induce prolonged NF-κB activation compared with TNF (26).…”

Section: The Role Of Tumor Necrosis Factor-like Weak Inducer Of Apoptmentioning

confidence: 99%

Section: Inf Lammatory Response Of Monocytes/macrophagesmentioning

confidence: 99%

See 1 more Smart Citation

The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors

Liu

Lin

Xiang

et al. 2017

Experimental and Therapeutic Medicine

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“…Unveiling the role of cytokines as inflammatory messengers provided a potential mechanism, whereby risk factors for atherosclerosis can alter arterial wall and produce a systemic response that favors atherothrombotic events (3). TNF-like weak inducer of apoptosis (TWEAK) participates through its sole receptor fibroblast growth factor-inducible 14 (Fn14) in several cellular responses associated with atherosclerosis (4). Experimental studies have shown a key role of the TWEAK-Fn14 axis in atherosclerotic plaque development, progression, and rupture (5-7).…”

Section: Introductionmentioning

confidence: 99%

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Fernández‐Laso

Sastre

Valdivielso

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Soluble TNF-like weak inducer of apoptosis (sTWEAK) is a proinflammatory cytokine belonging to the TNF superfamily. sTWEAK concentrations have been associated with the presence of CKD and cardiovascular disease (CVD). We hypothesized that sTWEAK levels may relate to a higher prevalence of atherosclerotic plaques, vascular calcification, and cardiovascular outcomes observed in patients with CKD.Design, setting, participants, & measurements A 4-year prospective, multicenter, longitudinal study was conducted in 1058 patients with CKD stages 3-5D (mean age =58613 years old; 665 men) but without any history of CVD from the NEFRONA Study (a study design on the prevalence of surrogate markers of CVD). Anklebrachial index and B-mode ultrasound were performed to detect the presence of carotid and/or femoral atherosclerotic plaques together with biochemical measurements and sTWEAK assessment. Patients were followed for cardiovascular outcomes (follow-up of 3.1361.15 years).Results Patients with more advanced CKD had lower sTWEAK levels. sTWEAK concentrations were independently and negatively associated with carotid intima-media thickness. sTWEAK levels were lower in patients with carotid atherosclerotic plaques but not in those with femoral plaques. After adjustment by confounders, the odds ratio (OR) for presenting carotid atherosclerotic plaques in patients in the lowest versus highest tertile of sTWEAK was 4.18 (95% confidence interval [95% CI], 2.89 to 6.08; P,0.001). Furthermore, sTWEAK levels were lower in patients with calcified carotid atherosclerotic plaques. The OR for presenting calcified carotid plaques was 1.77 (95% CI, 1.06 to 2.93; P=0.02) after multivariable adjustment. After the followup, 41 fatal and 68 nonfatal cardiovascular events occurred. In a Cox model, after controlling for potential confounding factors, patients in the lowest tertile of sTWEAK concentrations had a higher risk of fatal and nonfatal cardiovascular events (hazard ratio [HR], 2.40; 95% CI, 1.33 to 4.33; P=0.004) and cardiovascular mortality (HR, 2.67; 95% CI, 1.05 to 6.76; P=0.04).Conclusions Low sTWEAK levels were associated with the presence of carotid atherosclerotic plaques in patients with CKD. Additionally, lower sTWEAK levels were associated with a higher risk of cardiovascular morbidity and mortality.

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“…This, a member of TNF family, is synthesized as a type II transmembrane glycoprotein and circulates in plasma as a soluble form (sTWEAK) [11]. This molecule can induces smooth muscle cells proliferation in the arterial wall [12] and seems to be involved in all pathogenetic phases of ATS [13].…”

Section: Introductionmentioning

confidence: 99%

Nitroglycerin mediated dilation evaluated by ultrasound is associated with sTWEAK in hemodialysis patients.

Rusu

Ghervan

Racasan³

et al. 2016

Med Ultrason

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Aims: The main cause of death in hemodialysis (HD) patients is cardiovascular disease. Ultrasound assessment of the brachial artery dysfunction is easily achievable and can non-invasively detect atherosclerosis in various stages. In HD patients the cardiovascular risk profile is different and the determinants of brachial arterial function can be distinct comparing with general population. The aim of the study is to assess the determinants of arterial brachial function (flow-mediated and nitroglycerinmediated dilation) evaluated by ultrasound in HD patients and their relation with tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) described as atherosclerotic marker in chronic kidney disease patients. Material and methods: We conducted a cross-sectional observational study on 54 hemodialysis patients. We recorded clinical and biological data and we measured sTWEAK serum levels by ELISA. We evaluated the arterial brachial function by measurement of flow-mediated and nitroglycerin-mediated dilation, using B mode ultrasound. Results: The determinants of flow-mediated dilation were: Kt/V (r=0.47, p<0.001), LDL-cholesterol (r=0.29, p=0.04), and total cholesterol (r=0.31, p=0.02). Flow-mediated dilation correlated with nitroglycerin-mediated dilation (r=0.70, p<0.001). In multivariate analysis kt/V was the only significant predictor for flow-mediated dilation (p=0.04). Nitroglycerin-mediated dilation correlates with sTWEAK (r=-0.30, p=0.03), systolic blood pressure (r=-0.28, p=0.04) and pulse pressure (r=-0.31, p=0.02). In multivariate analysis sTWEAK was the only significant predictor for nitroglycerin-mediated dilation (p=0.04). Conclusions: The main determinant of nitroglycerin-mediated dilation was sTWEAK. In addition, decreased nitroglycerin-mediated dilation was associated with higher systolic blood pressure and pulse pressure. The main determinant of FMD was Kt/V. Increased flow-mediated dilation was associated with better dialysis efficiency and high total cholesterol and LDL-cholesterol.

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TWEAK/Fn14 Axis: A Promising Target for the Treatment of Cardiovascular Diseases

Cited by 67 publications

References 126 publications

The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors

The role of tumor necrosis factor-like weak inducer of apoptosis in atherosclerosis via its two different receptors

Soluble TWEAK and Major Adverse Cardiovascular Events in Patients with CKD

Nitroglycerin mediated dilation evaluated by ultrasound is associated with sTWEAK in hemodialysis patients.

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