Luchtefeld, Maren and Schunkert, Heribert and Stoll, Monika and Selle, Tina and Lorier, Rachel and Grote, Karsten and Sagebiel, Christian and Jagavelu, Kumaravelu and Tietge, Uwe J. E. and Assmus, Ulrike and Streetz, Konrad and Hengstenberg, Christian and Fischer, Marcus and Mayer, Bjoern and Maresso, Karen and El Mokhtari, Nour Eddine and Schreiber, Stefan and Mueller, Werner and Bavendiek, Udo and Grothusen, Christina and Drexler, Helmut and Trautwein, Christian and Broeckel, Ulrich and Schieffer, Bernhard (2007) Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man. JOURNAL OF EXPERIMENTAL MEDICINE, 204 (8). pp. 1935-1944. ISSN 0022-1007,
Full text not available from this repository. (Request a copy)Abstract
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 UST 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-REACTIVE PROTEIN; SERUM AMYLOID-A; CORONARY-ARTERY-DISEASE; E-DEFICIENT MICE; APOLIPOPROTEIN-E; MYOCARDIAL-INFARCTION; EXPRESSION; CHEMOATTRACTANT; INTERLEUKIN-6; CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 14:27 |
| Last Modified: | 01 Dec 2020 14:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32396 |
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