Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man.
Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man.
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炎症信号转导器 gp130 调节小鼠和人的动脉粥样硬化。
DOI：
10.1084/jem.20070120
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发表时间：
2007-08-06
期刊：
影响因子：
--
通讯作者：
Schieffer B
中科院分区：
文献类型：
--
作者：
Luchtefeld M;Schunkert H;Stoll M;Selle T;Lorier R;Grote K;Sagebiel C;Jagavelu K;Tietge UJ;Assmus U;Streetz K;Hengstenberg C;Fischer M;Mayer B;Maresso K;El Mokhtari NE;Schreiber S;Müller W;Bavendiek U;Grothusen C;Drexler H;Trautwein C;Broeckel U;Schieffer B
Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepatocytes, influences the risk of atherosclerosis in a hepatocyte-specific gp130 knockout. Mice on an atherosclerosis-prone genetic background exhibit less aortic atherosclerosis (P < 0.05) with decreased plaque macrophages (P < 0.01). Translating these findings into humans, we show that genetic variation within the human gp130 homologue, interleukin 6 signal transducer (IL6ST), is significantly associated with coronary artery disease (CAD; P < 0.05). We further show a significant association of atherosclerotic disease at the ostium of the coronary arteries (P < 0.005) as a clinically important and heritable subphenotype in a large sample of families with myocardial infarction (MI) and a second independent population–based cohort. Our results reveal a central role of a hepatocyte-specific, gp130-dependent acute phase reaction for plaque development in a murine model of atherosclerosis, and further implicate IL6ST as a genetic susceptibility factor for CAD and MI in humans. Thus, the acute phase reaction should be considered an important target for future drug development in the management of CAD.
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影响因子：
30.8
作者：
Broeckel, U;Hengstenberg, C;Schunkert, H
通讯作者：
Schunkert, H
影响因子：
9.8
作者：
Abecasis, GR;Cardon, LR;Cookson, WOC
通讯作者：
Cookson, WOC
动脉粥样硬化的炎症。
DOI：
10.1161/atvbaha.108.179705
发表时间：
2012-09
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Libby P
通讯作者：
Libby P
影响因子：
3.8
作者：
KU, NO;MORTENSEN, RF
通讯作者：
MORTENSEN, RF
影响因子：
4.1
作者：
Schaper, F;Gendo, C;Heinrich, PC
通讯作者：
Heinrich, PC