期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 528, 期 2, 页码 127-133出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2012.09.007
关键词
Interleukin 6; Prolyl-4-hydroxylase alpha 1; c-Jun; ERK1/2; Atherosclerosis
资金
- National Basic Research Program of China (973 Program) [2010CB732605, 2011CB503906]
- HI-TECH Technique and Development Program of China (863 Program) [2007AA02Z448]
- National Science Foundation of China [30728025, 30970709]
- Science Program of Shandong Province [2006GG2202039]
Interleukin 6 (IL-6) is a pivotal cytokine that regulates extracellular matrix metabolism by ameliorating the modification of collagen content, important in fibrous caps of atherosclerotic plaque. Prolyl-4-hydroxylase alpha 1 (P4H alpha 1) is a key intracellular enzyme required for synthesis of collagen in animals. We investigated the relationship of IL-6 and P4H alpha 1 in atherosclerosis-prone mice and human aortic smooth muscle cells (HASMCs). Apolipoprotein E (ApoE)-/- mice were fed a high-fat diet and a perivascular constrictive silica collar was placed on the right common carotid artery to induce atherosclerotic lesions, then mice were divided into two groups for transfection with empty lentivirus or IL-6 lentivirus. HASMCs were transfected with small interfering RNA or treated with recombinant human IL-6. IL-6 significantly downregulated collagen, P4H alpha 1 and smooth muscle cell contents in atherosclerotic mouse arteries. Macrophage and lipid contents in the atherosclerotic area were significantly increased with IL-6 treatment. IL-6 significantly downregulated P4H alpha 1 expression in HASMCs through an RAF-MEK1/2-ERK1/2 mitogen-activated protein kinase (MAPK) pathway, and c-Jun was involved in the process. Our findings highlight IL-6 destabilize atherosclerotic plaques in mice by downregulating P4H alpha 1 via an RAF-MEK1/2-ERK1/2 MAPK and c-Jun pathway. (C) 2012 Elsevier Inc. All rights reserved.
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