CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice
| Autor: | Christoph Knosalla, Fatemeh Kashani, Karl J. Lackner, Philipp S. Wild, Siyer Roohani, Andreas Daiber, Esther Lutgens, Sebastian Steven, Steffen Daub, Christian Becker, Beate Niesler, Yves Gramlich, Michael Hausding, Matthias Oelze, Swenja Kröller-Schön, Mobin Dib, Thomas Münzel, Eberhard Schulz, Alina Hanf, Hartmut Kleinert |
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| Přispěvatelé: | Other departments |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Physiology Anti-Inflammatory Agents Nitric Oxide Synthase Type II 030204 cardiovascular system & hematology Weight Gain medicine.disease_cause Antioxidants chemistry.chemical_compound 0302 clinical medicine Hyperlipidemia Endothelial dysfunction Mice Knockout biology Leptin Lipids Vasodilation Nitric oxide synthase Inflammation Mediators medicine.symptom Cardiology and Cardiovascular Medicine medicine.medical_specialty CD40 Ligand Hyperlipidemias Inflammation Diet High-Fat 03 medical and health sciences Physiology (medical) Internal medicine medicine Animals Humans Obesity Platelet activation TNF Receptor-Associated Factor 6 Interleukin-6 Cholesterol business.industry Myocardium NADPH Oxidases Platelet Activation medicine.disease Mice Inbred C57BL Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 chemistry biology.protein Endothelium Vascular business Biomarkers Oxidative stress |
| Zdroj: | Cardiovascular research, 114(2), 312-323. Oxford University Press |
| ISSN: | 1755-3245 0008-6363 |
| Popis: | Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L expression, weight, leptin and lipids were increased, and endothelial dysfunction, oxidative stress and inflammation were more pronounced in wild type mice on a high fat diet, all of which was almost normalized by CD40L deficiency. Similar results were obtained in diabetic db/db mice with CD40/TRAF6 inhibitor (6877002) therapy. In a small human study higher serum sCD40L levels and an inflammatory phenotype were detected in the blood and Aorta ascendens of obese patients (body mass index > 35) that underwent by-pass surgery. Conclusion CD40L controls obesity-associated vascular inflammation, oxidative stress and endothelial dysfunction in mice and potentially humans. Thus, CD40L represents a therapeutic target in lipid metabolic disorders which is a leading cause in cardiovascular disease. |
| Databáze: | OpenAIRE |
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