13 research outputs found
Book Review: Challenges to Federalism: Policy-Making in Canada and the Federal Republic of Germany: Challenges to Federalism: Policy-Making in Canada and the Federal Republic of Germany ChandlerWilliam M. et ZöllnerChristian W., eds. Kingston: Institute of Intergovernmental Relations, Queen's University, 1989, 300 p
Mid-term results of interventional closure of patent foramen ovale with the Occlutech Figulla® Flex II Occluder
Transsignaling of Interleukin-6 Crucially Contributes to Atherosclerosis in Mice
Objective-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. Methods and Results-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. Conclusion-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. (Arterioscler Thromb Vasc Biol. 2012;32:281-290.