期刊
VASCULAR PHARMACOLOGY
卷 85, 期 -, 页码 1-10出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2015.08.012
关键词
AMPK; Macrophage; oxLDL uptake; LOX-1; Atherosclerosis
资金
- National Natural Sciences Foundation of China (NSFC) [81273514, 91229127]
- Specialized Research Fund for the Doctoral Program of Higher Education [20121106110032]
- Beijing Talents Funding-Project A [2011A009008000004]
- National ST Major Project [2012ZX09301002-004, 2012ZX09102101-020, 2012ZX09301002-002]
The differentiation of macrophages into lipid-laden foam cells is a hallmark in early-stage atherosclerosis. The developmental role of adenosine monophosphate-activated protein kinase (AMPK) in a transformation of foam cells, especially in macrophage cholesterol uptake that remains undetermined. Here we demonstrate that AMPK activation in response to IMM-H007 or AICAR resulted in a decrease in macrophage cholesterol uptake and thus inhibited foam cell formation in macrophages mediated by oxidized low-density lipoprotein (oxLDL). This functional change was caused by a downregulation of mRNA and protein expression of LOX-1 but not other scavenger receptors, including scavenger receptor-A (SR-A), CD36 and scavenger receptor-BI (SR-BI). The expression of LOX-1 was regulated by AMPK activation induced decreased phosphorylation of nuclear transcription factor NF-kappa B, since siRNA interference or dominant negative AMPK overexpression significantly promotes Ser536 dephosphorylation of NF-kappa B p65 and thus increases LOX-1 expression. Moreover, pharmacological AMPK activation was shown to promote protein phosphatase 2A (PP2A) activity and the specific PP2A inhibitor, okadaic acid, could prevent the effects of IMM-H007 or AICAR on NF-kappa B and LOX-1. In vivo, pharmacological AMPK activation reduced the lesion size of atherosclerosis and the expression of LOX-1 in aortas in apolipoprotein E-deficient mice. Our current findings suggest a novel mechanism of LOX-1 regulation by AMPI(to attenuate macrophage oxLDL uptake and atherosclerosis. (C) 2016 Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据