Molecular link between cholesterol, cytokines and atherosclerosis
Molecular link between cholesterol, cytokines and atherosclerosis
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胆固醇、细胞因子和动脉粥样硬化之间的分子联系
DOI：
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发表时间：
2001
影响因子：
4.3
通讯作者：
D. Kaul
中科院分区：
文献类型：
--
作者：
D. Kaul
目前对动脉粥样硬化起源的研究引发了一场激烈的争论，即动脉粥样硬化是由高胆固醇血症还是对血管损伤的不适当免疫反应引起的。尽管免疫系统的作用受到质疑，但大量证据清楚地表明，动脉粥样硬化是由胆固醇与细胞分泌的细胞因子（尤其是IL-6）和载脂蛋白“E”之间的相互作用引发的。最近的研究表明，细胞具有两种胆固醇传感器：(a)受体- ck，它感知细胞外胆固醇并启动信号通路，负责调节参与细胞周期、细胞死亡、细胞胆固醇稳态和细胞因子（包括IL-6）的基因；(b) LxRα，它感知细胞内的氧甾醇，并控制参与细胞死亡、细胞胆固醇稳态和细胞因子IL-8的基因。这些胆固醇传感器定义了胆固醇依赖性调节动脉壁内细胞合成和细胞因子（IL-6、IL-8）分泌的分子机制。基于这一机制，胆固醇及其氧衍生物在修饰LDL中的存在会导致受体- ck依赖基因的短暂激活/失活，从而引起生长与凋亡的反复循环，导致动脉壁中凋亡缺陷细胞被选中，导致其积累和形成寡克隆动脉粥样硬化斑块。
Current investigation on the origin of atherosclerosis has initiated an intense debate over whether atherosclerosis results from hypercholesterolemia or an inappropriate immune response to vascular injury. Although the role of the immune system has been questioned, the overwhelming body of evidence clearly indicates that atherogenesis is initiated by the interplay between cholesterol and cellular secretion of cytokines (especially IL-6) and apolipoprotein ‘E’ within the arterial wall. Recent studies have revealed that cells possess two cholesterol-sensors: (a) Receptor-Ck which senses the extracellular cholesterol and initiates signalling pathway responsible for the regulation of genes involved in the cell cycle, cell death, cellular cholesterol homeostasis and cytokines including IL-6; (b) LxRα which senses intracellular oxysterols and controls genes involved in cell death, cellular cholesterol homeostasis and cytokine IL-8. These cholesterol sensors define the molecular mechanism responsible for cholesterol-depended regulation of cellular synthesis and secretion of cytokines (IL-6, IL-8) within arterial wall. On the basis of this mechanism, presence of cholesterol and its oxy-derivative in the modified LDL will result in transient activation/deactivation of Receptor-Ck-dependent genes which will give rise to repeated cycles of growth coupled with apoptosis leading to a situation where apoptotic-deficient cells in the arterial wall, would be selected resulting in their accumulation and formation of oligoclonal atherosclerotic plaque.
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IL-6 和 CD40 信号传导之间的关联。
DOI：
--
发表时间：
1990
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Clark,EA;Shu,G
通讯作者：
Shu,G
DOI：
10.1073/pnas.86.4.1372
发表时间：
1989-02-01
影响因子：
11.1
作者：
PALINSKI, W;ROSENFELD, ME;WITZTUM, JL
通讯作者：
WITZTUM, JL
影响因子：
56.9
作者：
BROWN, MS;GOLDSTEIN, JL
通讯作者：
GOLDSTEIN, JL
DOI：
10.1073/pnas.83.14.5214
发表时间：
1986-07-01
影响因子：
11.1
作者：
TSUJIMOTO, Y;CROCE, CM
通讯作者：
CROCE, CM
氧化 LDL 增强巨噬细胞 apoE 分泌的机制。
影响因子：
6.5
作者：
Cader,AA;Steinberg,FM;Mazzone,T;Chait,A
通讯作者：
Chait,A