P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation.
P2X7R is involved in the progression of atherosclerosis by promoting NLRP3 inflammasome activation.
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DOI：
10.3892/ijmm.2015.2129
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发表时间：
2015-05
影响因子：
5.4
通讯作者：
Qu P
中科院分区：
文献类型：
--
作者：
Peng K;Liu L;Wei D;Lv Y;Wang G;Xiong W;Wang X;Altaf A;Wang L;He D;Wang H;Qu P
嘌呤能2X 7受体（P2 X7 R）和核苷酸结合寡聚化结构域样受体蛋白3（NLRP 3）在动脉粥样硬化病变的巨噬细胞中表达。然而，P2 X7 R参与动脉粥样硬化炎症反应的机制在很大程度上仍然未知。本研究的目的是探讨P2 X7 R在动脉粥样硬化中的作用以及氧化低密度脂蛋白（oxLDL）刺激后NLRP 3炎性体的作用机制。我们通过免疫组织化学和免疫荧光染色观察了P2 X7 R在尸检标本冠状动脉粥样硬化斑块和apoE−/−小鼠主动脉窦中的表达和分布。利用短干扰RNA（siRNA）的特异性来抑制P2 X7 R和NLRP 3 mRNA的表达。RT-qPCR和蛋白质印迹分析分别用于分析mRNA和蛋白质表达。免疫共沉淀用于检查蛋白激酶R（PKR）磷酸化和NLRP 3之间的相互作用。P2 X7 R和NLRP 3在冠状动脉粥样硬化斑块中高水平表达。oxLDL刺激可上调P2 X7 R、NLRP 3和白细胞介素（IL）-1β的表达。通过siRNA敲低P2 X7 R，通过抑制oxLDL介导的PKR磷酸化来抑制NLRP 3炎性体活化。在apoE−/−小鼠主动脉窦的动脉粥样硬化病变中，发现P2 X7 R表达水平较高。此外，P2 X7 R siRNA减弱了apoE−/−小鼠动脉粥样硬化的发展。总之，我们的研究结果表明，P2 X7 R在动脉粥样硬化的发展中起着重要的作用，并通过促进PKR磷酸化调节NLRP 3炎性小体激活。
Purinergic 2X7 receptor (P2X7R) and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) are expressed in macrophages in atherosclerotic lesions. However, the mechanisms through which P2X7R participates in the inflammatory response in atherosclerosis remain largely unknown. The aim of the present study was to investigate the role of P2X7R in atherosclerosis and the mechanisms of action of the NLRP3 inflammasome following stimulation with oxidized low-density lipoprotein (oxLDL). We observed the expression and distribution of P2X7R in the atherosclerotic plaque in the coronary arteries from an autopsy specimen and in that of the aortic sinuses of apoE−/− mice by immunohistochemistry and immunofluorescence staining. The specificity of short interfering RNA (siRNA) was used to suppress P2X7R and NLRP3 mRNA expression. RT-qPCR and western blot analysis were used to analyze mRNA and protein expression, respectively. Co-immunoprecipitation was used to examine the interaction between protein kinase R (PKR) phosphorylation and NLRP3. P2X7R and NLRP3 were expressed at high levels in the atherosclerotic plaque in the coronary arteries. Stimulation with oxLDL upregulated P2X7R, NLRP3 and interleukin (IL)-1β expression. P2X7R knockdown by siRNA suppressed NLRP3 inflammasome activation by inhibiting the PKR phosphorylation mediated by oxLDL. In the atherosclerotic lesions in the aortic sinuses of apoE−/− mice, P2X7R expression was found at high levels. Moreover, P2X7R siRNA attenuated the development of atherosclerosis in the apoE−/− mice. In conclusion, our results demonstrate that P2X7R plays a significant role in the development of atherosclerosis and regulates NLRP3 inflammasome activation by promoting PKR phosphorylation.
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影响因子：
3.7
作者：
Rajamäki K;Lappalainen J;Oörni K;Välimäki E;Matikainen S;Kovanen PT;Eklund KK
通讯作者：
Eklund KK
影响因子：
5
作者：
Grebe, Alena;Latz, Eicke
通讯作者：
Latz, Eicke
影响因子：
15.9
作者：
Mullick, AE;Tobias, PS;Curtiss, LK
通讯作者：
Curtiss, LK
影响因子：
30.5
作者：
通讯作者：
--
影响因子：
37.8
作者：
Ehara, S;Ueda, M;Becker, AE
通讯作者：
Becker, AE