ArticlePloS one2017
Interaction of IL-6 and TNF-α contributes to endothelial dysfunction in type 2 diabetic mouse hearts.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 4 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 4 syntheses or guidelines pooled it, 125 citations in OpenAlex.
- Association between diabetic kidney disease and visceral adiposity index: a meta-analysis.BMC nephrology · 2026Pooled it
- Deciphering the Role of Sirtuin-1 Gene Polymorphism in Diabetic Nephropathy: A Systematic Review and Meta-Analysis.Journal of diabetes research · 2026Pooled it
- The effect of Tai Chi on glycemic control in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials.Frontiers in endocrinology · 2025Pooled it
- Meta-analysis: Interleukin 6 gene -174G/C polymorphism associated with type 2 diabetes mellitus and interleukin 6 changes.Journal of cellular and molecular medicine · 2021Pooled it
- Optimizing early triage for subclinical cardiovascular-kidney-metabolic syndrome: longitudinal associations, incremental value, and clinical utility of nine insulin resistance surrogates.Cardiovascular diabetology · 2026Article
- Review
- Prognostic value of stress hyperglycemia ratio, hemoglobin glycation index, and glycemic variability for postoperative atrial fibrillation: a machine learning-based prediction model.BMC medical informatics and decision making · 2026Article
- Quercetin Improves Cognitive Function by Ameliorating Histopathological Changes and Inflammation in Di(2-ethylhexyl) Phthalate-Exposed Mice.Brain sciences · 2026Article
- Modulation of the gut-heart axis by exercise in diabetic cardiomyopathy: Microbial mechanisms and clinical implications.iScience · 2026Review
- Low serum dehydroepiandrosterone sulfate is related to diabetic retinopathy in males with type 2 diabetes mellitus.Journal of translational medicine · 2026Article
- Epigenetic regulation by HDAC11-driven STAT3 activation promotes pro-inflammatory cytokine production and endothelial dysfunction upon bacterial infection in diabetes.Cell communication and signaling : CCS · 2026Article
- NMN protects vascular endothelial cells from M1 macrophage-derived IL-1β-induced hyperpermeability by inhibiting VE-cadherin degradation.Frontiers in cardiovascular medicine · 2026Article
- A large-scale profiling study of immune-coagulation associations in rheumatoid arthritis.Frontiers in immunology · 2026Article
- Experimental Models for Studying Cardiovascular Dysfunction in Metabolic Syndrome.Handbook of experimental pharmacology · 2026Review
- The Association of Diabetes and Atherosclerosis: Understanding the Molecular Mechanism of the Double Burden.Current medicinal chemistry · 2026Review
- Angiogenic Potential of Small Extracellular Vesicles Produced by Stimulated Mesenchymal Stromal Cells Under Hypoxic Conditions.Journal of extracellular biology · 2026Article
- Review
- Post-Traumatic Stress Disorder (PTSD) and Cardiovascular Diseases: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2025Review
- Fat distribution, inflammatory mechanisms, and cardiovascular disease risk: mediation analysis based on the Framingham risk score.BMC cardiovascular disorders · 2025Article
- Epicardial Adipose Tissue-A Novel Therapeutic Target in Obesity Cardiomyopathy.International journal of molecular sciences · 2025Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesInflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), are individually considered as important contributors to endothelial dysfunction in obesity and type 2 diabetes (T2D). However, their interactions in coronary arteriole endothelial dysfunction are uncertain. Therefore, this study aimed to determine the effects of TNF-α and IL-6 interactions on coronary endothelial dysfunction in experimental T2D.
methodsThe studies used wild type (WT), diabetic mice (db/db), db/db null for TNF (dbTNF-/dbTNF-), and db/db mice treated with neutralizing antibody to IL-6 (anti-IL-6). Endothelium-dependent (acetylcholine [ACh], or luminal flow-induced shear stress) and endothelium-independent (sodium nitroprusside [SNP]) vasodilation of isolated and pressurized coronary arterioles were determined. Quantitative PCR, Western blot, and immunofluorescence staining were utilized for mechanistic studies.
resultsRelative to WT, arteriolar dilation to both ACh and flow was attenuated in db/db mice and dbTNF-/dbTNF-. Treatment of dbTNF-/dbTNF- and db/db mice with anti-IL-6 improved arteriolar dilation compared to db/db mice. Immunofluorescence staining illustrated localization of IL-6 within the endothelial cells of coronary arterioles. In db/db mice, mRNA and protein expression of IL-6 and superoxide (O2-) production were higher, but reduced by anti-IL-6 treatment. Also, in db/db mice, mRNA and protein expression of TNF-α suppressed by the anti-IL-6 treatment and the reduced expression of mRNA and protein expression of IL-6 by the genetic deletion of TNF-α both supported a reciprocal regulation between TNF-α and IL-6. Superoxide dismutase 2 (SOD2) expression and phosphorylation of eNOS (p-eNOS/eNOS) were lower in db/db mice coronary arterioles and were restored in db/db+Anti-IL-6 and dbTNF-/dbTNF- mice.
conclusionThe interactions between TNF-α and IL-6 exacerbate oxidative stress and reduce phosphorylation of eNOS, thereby contributing to coronary endothelial dysfunction in T2D mice.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.