PI3K regulates the activation of NLRP3 inflammasome in atherosclerosis through part-dependent AKT signaling pathway.
PI3K regulates the activation of NLRP3 inflammasome in atherosclerosis through part-dependent AKT signaling pathway.
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PI3K通过部分依赖的AKT信号通路调控动脉粥样硬化中NLRP3炎性体的激活。
DOI：
10.1538/expanim.21-0002
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发表时间：
2021-11-10
影响因子：
2.4
通讯作者：
Qu P
中科院分区：
文献类型：
--
作者：
Liu Z;Li J;Lin S;Wu Y;He D;Qu P
PI 3 K是多种细胞表面受体的下游靶标，其充当细胞极化和存活的关键调节剂。PI 3 K/AKT信号通路通常参与癌症、动脉粥样硬化等疾病的发生。然而，它在心血管疾病，特别是动脉粥样硬化中的作用仍有待进一步研究。为了确定PI 3 K/AKT信号通路对细胞炎症反应和氧化应激的影响，使用PI 3 K抑制剂（GDC 0941）和AKT抑制剂（MK 2206）。首先，将THP-1细胞与ox-LDL（100 μg/ml）孵育以建立体外动脉粥样硬化模型。然后评价炎症因子和泡沫细胞形成以确定和比较PI 3 K和AKT抑制的效果。ApoE−/−小鼠喂食高脂饮食，用于评估PI 3 K和AKT在主动脉斑块形成中的作用。我们的研究结果表明，抑制PI 3 K或AKT可以抑制NLRP 3的活化，降低p-p65/p65的表达水平，减少线粒体反应氧（mitoROS）的产生。抑制PI 3 K或AKT也可减少ApoE−/−小鼠动脉粥样硬化病变和斑块面积，并降低NLRP 3和IL-1β水平。抑制PI 3 K的作用比抑制AKT的作用更显著。因此，抑制PI 3 K可以延缓动脉粥样硬化的进展。此外，可能还有其他AKT非依赖性途径调节动脉粥样硬化的形成。
PI3K is a downstream target of multiple cell-surface receptors, which acts as a crucial modulator of both cell polarization and survival. PI3K/AKT signaling pathway is commonly involved in cancer, atherosclerosis, and other diseases. However, its role in cardiovascular diseases, especially in atherosclerosis, remains to be further investigated. To determine the effect of PI3K/AKT signaling pathway on cellular inflammatory response and oxidative stress, PI3K inhibitor (GDC0941) and AKT inhibitor (MK2206) were used. First, THP-1 cells were incubated with ox-LDL (100 µg/ml) to establish an in vitro atherosclerosis model. The inflammatory factors and foam cell formation were then evaluated to ascertain and compare the effects of PI3K and AKT inhibition. ApoE−/− mice fed a high-fat diet were used to assess the roles of PI3K and AKT in aortic plaque formation. Our results showed that the inhibition of PI3K or AKT could suppress the activation of NLRP3, decreased the expression levels of p-p65/p65 and reduced the production of mitochondrial reaction oxygen species (mitoROS) in THP-1 cells. Inhibition of PI3K or AKT could also reduced atherosclerosis lesion and plaque area, and decreased the levels of NLRP3 and IL-1β in ApoE−/− mice. The effect of PI3K inhibition was more significant than AKT. Therefore, PI3K inhibition can retard the progress of atherosclerosis. Besides, there may be other AKT-independent pathways that regulate the formation of atherosclerosis.
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影响因子：
4.4
作者：
Karasawa T;Takahashi M
通讯作者：
Takahashi M
影响因子：
30.5
作者：
Koelwyn GJ;Corr EM;Erbay E;Moore KJ
通讯作者：
Moore KJ
DOI：
10.4049/jimmunol.1102488
发表时间：
2012-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Allen IC;Jania CM;Wilson JE;Tekeppe EM;Hua X;Brickey WJ;Kwan M;Koller BH;Tilley SL;Ting JP
通讯作者：
Ting JP
DOI：
10.1038/nri3520
发表时间：
2013-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A