Arteriosclerosis, thrombosis, and vascular biology, 2012-02, Vol.32 (2), p.281
2012
Details
- Autor(en) / Beteiligte
- Titel
- Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2012-02, Vol.32 (2), p.281
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Transsignaling of interleukin (IL)-6 is a central pathway in the pathogenesis of disorders associated with chronic inflammation, such as Crohn disease, rheumatoid arthritis, and inflammatory colon cancer. Notably, IL-6 also represents an independent risk factor for coronary artery disease (CAD) in humans and is crucially involved in vascular inflammatory processes. In the present study, we showed that treatment with a fusion protein of the natural IL-6 transsignaling inhibitor soluble glycoprotein 130 (sgp130) and IgG1-Fc (sgp130Fc) dramatically reduced atherosclerosis in hypercholesterolemic Ldlr(-/-) mice without affecting weight gain and serum lipid levels. Moreover, sgp130Fc treatment even led to a significant regression of advanced atherosclerosis. Mechanistically, endothelial activation and intimal smooth muscle cell infiltration were decreased in sgp130Fc-treated mice, resulting in a marked reduction of monocyte recruitment and subsequent atherosclerotic plaque progression. Of note, patients with CAD exhibited significantly lower plasma levels of endogenous sgp130, suggesting that a compromised counterbalancing of IL-6 transsignaling may contribute to atherogenesis in humans. These data clarify, for the first time, the critical involvement of, in particular, the transsignaling of IL-6 in CAD and warrant further investigation of sgp130Fc as a novel therapeutic for the treatment of CAD and related diseases.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1524-4636DOI: 10.1161/ATVBAHA.111.229435Titel-ID: cdi_pubmed_primary_22075248
- Format
- –
- Schlagworte
- Aged, Animals, Atherosclerosis - physiopathology, Atherosclerosis - prevention & control, Coronary Artery Disease - blood, Coronary Artery Disease - physiopathology, Coronary Artery Disease - prevention & control, Cytokine Receptor gp130 - blood, Cytokine Receptor gp130 - pharmacology, Cytokine Receptor gp130 - therapeutic use, Disease Models, Animal, Disease Progression, Female, Humans, Hypercholesterolemia - blood, Hypercholesterolemia - physiopathology, Interleukin-6 - physiology, Lipids - blood, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Receptors, LDL - deficiency, Receptors, LDL - genetics, Recombinant Fusion Proteins - pharmacology, Recombinant Fusion Proteins - therapeutic use, Signal Transduction - drug effects, Signal Transduction - physiology