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Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice

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Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. / Schuett, Harald; Oestreich, René; Waetzig, Georg H; Annema, Wijtske; Luchtefeld, Maren; Hillmer, Anja; Bavendiek, Udo; von Felden, Johann; Divchev, Dimitar; Kempf, Tibor; Wollert, Kai C; Seegert, Dirk; Rose-John, Stefan; Tietge, Uwe J F; Schieffer, Bernhard; Grote, Karsten.

In: ARTERIOSCL THROM VAS, Vol. 32, No. 2, 02.2012, p. 281-90.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schuett, H, Oestreich, R, Waetzig, GH, Annema, W, Luchtefeld, M, Hillmer, A, Bavendiek, U, von Felden, J, Divchev, D, Kempf, T, Wollert, KC, Seegert, D, Rose-John, S, Tietge, UJF, Schieffer, B & Grote, K 2012, 'Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice', ARTERIOSCL THROM VAS, vol. 32, no. 2, pp. 281-90. https://doi.org/10.1161/ATVBAHA.111.229435

APA

Schuett, H., Oestreich, R., Waetzig, G. H., Annema, W., Luchtefeld, M., Hillmer, A., Bavendiek, U., von Felden, J., Divchev, D., Kempf, T., Wollert, K. C., Seegert, D., Rose-John, S., Tietge, U. J. F., Schieffer, B., & Grote, K. (2012). Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. ARTERIOSCL THROM VAS, 32(2), 281-90. https://doi.org/10.1161/ATVBAHA.111.229435

Vancouver

Schuett H, Oestreich R, Waetzig GH, Annema W, Luchtefeld M, Hillmer A et al. Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. ARTERIOSCL THROM VAS. 2012 Feb;32(2):281-90. https://doi.org/10.1161/ATVBAHA.111.229435

Bibtex

@article{48293c661cd84926b39121076c7fa9d4,
title = "Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice",
abstract = "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.CONCLUSIONS: 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.",
keywords = "Aged, Animals, Atherosclerosis, Coronary Artery Disease, Cytokine Receptor gp130, Disease Models, Animal, Disease Progression, Female, Humans, Hypercholesterolemia, Interleukin-6, Lipids, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Receptors, LDL, Recombinant Fusion Proteins, Signal Transduction, Journal Article, Research Support, Non-U.S. Gov't",
author = "Harald Schuett and Ren{\'e} Oestreich and Waetzig, {Georg H} and Wijtske Annema and Maren Luchtefeld and Anja Hillmer and Udo Bavendiek and {von Felden}, Johann and Dimitar Divchev and Tibor Kempf and Wollert, {Kai C} and Dirk Seegert and Stefan Rose-John and Tietge, {Uwe J F} and Bernhard Schieffer and Karsten Grote",
year = "2012",
month = feb,
doi = "10.1161/ATVBAHA.111.229435",
language = "English",
volume = "32",
pages = "281--90",
journal = "ARTERIOSCL THROM VAS",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

RIS

TY - JOUR

T1 - Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice

AU - Schuett, Harald

AU - Oestreich, René

AU - Waetzig, Georg H

AU - Annema, Wijtske

AU - Luchtefeld, Maren

AU - Hillmer, Anja

AU - Bavendiek, Udo

AU - von Felden, Johann

AU - Divchev, Dimitar

AU - Kempf, Tibor

AU - Wollert, Kai C

AU - Seegert, Dirk

AU - Rose-John, Stefan

AU - Tietge, Uwe J F

AU - Schieffer, Bernhard

AU - Grote, Karsten

PY - 2012/2

Y1 - 2012/2

N2 - 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.CONCLUSIONS: 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.

AB - 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.CONCLUSIONS: 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.

KW - Aged

KW - Animals

KW - Atherosclerosis

KW - Coronary Artery Disease

KW - Cytokine Receptor gp130

KW - Disease Models, Animal

KW - Disease Progression

KW - Female

KW - Humans

KW - Hypercholesterolemia

KW - Interleukin-6

KW - Lipids

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Middle Aged

KW - Receptors, LDL

KW - Recombinant Fusion Proteins

KW - Signal Transduction

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1161/ATVBAHA.111.229435

DO - 10.1161/ATVBAHA.111.229435

M3 - SCORING: Journal article

C2 - 22075248

VL - 32

SP - 281

EP - 290

JO - ARTERIOSCL THROM VAS

JF - ARTERIOSCL THROM VAS

SN - 1079-5642

IS - 2

ER -