The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI.
The Inflammasome Signaling Pathway Is Actively Regulated and Related to Myocardial Damage in Coronary Thrombi from Patients with STEMI.
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DOI：
10.1155/2021/5525917
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发表时间：
2021
影响因子：
4.6
通讯作者：
Seljeflot I
中科院分区：
文献类型：
--
作者：
Nordeng J;Schandiz H;Solheim S;Åkra S;Hoffman P;Roald B;Bendz B;Arnesen H;Helseth R;Seljeflot I
Nod 样受体蛋白 3 (NLRP3) 炎症小体和白细胞介素 6 (IL-6) 通路是心肌再灌注损伤中炎症反应的核心机制。扩大我们对炎症体信号轴的了解对于改善治疗选择非常重要。在一项横断面研究中，我们旨在研究 ST 段抬高型心肌梗死 (STEMI) 患者冠状动脉血栓和循环白细胞中炎性体和 IL-6 信号传导相关蛋白的存在、定位和基因表达，以及与心肌损伤以及从出现症状到 PCI 的时间的关系。 从 33 名 STEMI 患者中抽吸出冠状动脉内血栓。抽取了血样。从血栓和循环白细胞中分离出 Toll 样受体 4 (TLR4)、NLRP3、半胱天冬酶 1、白细胞介素 1β (IL1-β)、白细胞介素 18 (IL-18)、IL-6、IL-6 受体 (IL-6R) 和糖蛋白 130 (gp130) 的 mRNA，并通过 RT-PCR 进行相对定量。将每个血栓的一部分包埋在石蜡中用于组织学和免疫组织化学分析。 编码这 8 个标记的基因存在于 76-100% 的血栓中。血栓中 TLR4 的表达与肌钙蛋白 T 显着相关（r = 0.455，p = 0.013），NLRP3 也是如此（r = 0.468，p = 0.024）。肌钙蛋白 T 与循环白细胞中 TLR4（r = 0.438，p = 0.011）、NLRP3（r = 0.420，p = 0.0149）和 IL-1β（r = 0.394，p = 0.023）的表达相关。血栓中的 IL-6R 表达与肌钙蛋白 T 显着相关（r = 0.434，p = 0.019），而 gp130 呈负相关（r = -0.398，p = 0.050）。循环白细胞中的 IL-6 与肌钙蛋白 T 呈反比（r = -0.421，p = 0.015）。血栓中表达的基因与从症状到 PCI 的时间之间没有显着相关性。 冠状动脉血栓和 STEMI 患者循环白细胞中的炎性体信号通路受到积极调节，与肌钙蛋白 T 测量的心肌损伤相关。这支持了医学上针对该通路治疗心肌梗死的策略，并有助于找出抗炎治疗的最佳时机和目标。该研究已在 ClinicalTrials.gov 上注册，识别号为 NCT02746822。
The Nod-Like-Receptor-Protein-3 (NLRP3) inflammasome and the Interleukin-6 (IL-6) pathways are central mechanisms of the inflammatory response in myocardial reperfusion injury. Expanding our knowledge about the inflammasome signaling axis is important to improve treatment options. In a cross-sectional study, we aimed to study presence, localization, and genetic expression of inflammasome- and IL-6- signaling-related proteins in coronary thrombi and circulating leukocytes from ST-elevation myocardial infarction (STEMI) patients, with relation to myocardial injury and time from symptoms to PCI. Intracoronary thrombi were aspirated from 33 STEMI patients. Blood samples were drawn. mRNA of Toll-Like-Receptor-4 (TLR4), NLRP3, caspase 1, Interleukin-1β (IL1-β), Interleukin-18 (IL-18), IL-6, IL-6-receptor (IL-6R), and glycoprotein 130 (gp130) were isolated from thrombi and circulating leukocytes and relatively quantified by RT-PCR. A part of each thrombus was embedded in paraffin for histology and immunohistochemistry analyses. Genes encoding the 8 markers were present in 76-100% of thrombi. Expression of TLR4 in thrombi significantly correlated to troponin T (r = 0.455, p = 0.013), as did NLRP3 (r = 0.468, p = 0.024). Troponin T correlated with expression in circulating leukocytes of TLR4 (r = 0.438, p = 0.011), NLRP3 (r = 0.420, p = 0.0149), and IL-1β (r = 0.394, p = 0.023). IL-6R expression in thrombi correlated significantly to troponin T (r = 0.434, p = 0.019), whereas gp130 was inversely correlated (r = −0.398, p = 0.050). IL-6 in circulating leukocytes correlated inversely to troponin T (r = −0.421, p = 0.015). There were no significant correlations between genes expressed in thrombi and time from symptom to PCI. The inflammasome signaling pathway was actively regulated in coronary thrombi and in circulating leukocytes from patients with STEMI, in association with myocardial damage measured by troponin T. This supports the strategy of medically targeting this pathway in treating myocardial infarction and contributes to sort out optimal timing and targets for anti-inflammatory treatment. The study is registered at clinicaltrials.gov with identification number NCT02746822.
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DOI：
10.1073/pnas.1716095115
发表时间：
2018-02-13
影响因子：
11.1
作者：
Marchetti C;Swartzwelter B;Gamboni F;Neff CP;Richter K;Azam T;Carta S;Tengesdal I;Nemkov T;D'Alessandro A;Henry C;Jones GS;Goodrich SA;St Laurent JP;Jones TM;Scribner CL;Barrow RB;Altman RD;Skouras DB;Gattorno M;Grau V;Janciauskiene S;Rubartelli A;Joosten LAB;Dinarello CA
通讯作者：
Dinarello CA
DOI：
10.1016/s2665-9913(20)30065-5
发表时间：
2020-05
期刊：
The Lancet. Rheumatology
影响因子：
--
作者：
Klück V;Jansen TLTA;Janssen M;Comarniceanu A;Efdé M;Tengesdal IW;Schraa K;Cleophas MCP;Scribner CL;Skouras DB;Marchetti C;Dinarello CA;Joosten LAB
通讯作者：
Joosten LAB
影响因子：
5.7
作者：
Champney, K. P.;Frederick, P. D.;Vaccarino, V.
通讯作者：
Vaccarino, V.
影响因子：
20.1
作者：
Ridker, Paul M.
通讯作者：
Ridker, Paul M.
影响因子：
39.3
作者：
Ibanez, Borja;James, Stefan;Zeymer, Uwe
通讯作者：
Zeymer, Uwe