The Fractalkine Receptor CX(3)CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling.
The Fractalkine Receptor CX(3)CR1 Links Lymphocyte Kinetics in CMV-Seropositive Patients and Acute Myocardial Infarction With Adverse Left Ventricular Remodeling.
复制标题
DOI：
10.3389/fimmu.2021.605857
复制
发表时间：
2021
影响因子：
7.3
通讯作者：
Spyridopoulos I
中科院分区：
文献类型：
--
作者：
Spray L;Park C;Cormack S;Mohammed A;Panahi P;Boag S;Bennaceur K;Sopova K;Richardson G;Stangl VM;Rech L;Rainer PP;Ramos GC;Hofmann U;Stellos K;Spyridopoulos I
潜伏性巨细胞病毒（CMV）感染与不良心血管结局相关。病毒特异性CX 3CR 1+效应记忆T细胞由于其促炎特性可能在此过程中起作用。我们研究了接受直接经皮冠状动脉介入治疗（pPCI）的ST段抬高型心肌梗死（STEMI）患者中CX 3CR 1（Fractalkine受体）在CMV相关淋巴细胞动力学和心脏重塑中的作用。我们回顾性分析了4874例STEMI/pPCI患者的淋巴细胞计数、肌钙蛋白和生存率，在前瞻性队列中评价了再灌注期间的淋巴细胞动力学，并获得了连续心脏MRI（cMRI）以评估重塑。再灌注前淋巴细胞减少独立预测7.5年时的死亡率。在再灌注之前，CCR 7 + T淋巴细胞似乎被耗尽。再灌注后，表达CX 3CR 1的T淋巴细胞主要在CMV血清阳性患者中耗尽。在缺血/再灌注期间，CX 3CR 1 + T淋巴细胞的下降与CMV+患者的微血管阻塞显著相关，表明Fractalkine-受体相互作用增加。在12周时，CMV+患者显示出不良的LV重构。我们发现淋巴细胞减少发生在ST段抬高型心肌梗死再灌注前后的不同机制，并可预测长期预后。在CMV+患者中，增加的Fractalkine诱导和CX 3CR 1 + T细胞的隔离可能有助于不良重塑，表明促炎病理机制，其提供了新的治疗靶点。
Latent cytomegalovirus (CMV) infection is associated with adverse cardiovascular outcomes. Virus-specific CX3CR1+ effector memory T-cells may be instrumental in this process due to their pro-inflammatory properties. We investigated the role of CX3CR1 (fractalkine receptor) in CMV-related lymphocyte kinetics and cardiac remodeling in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We retrospectively analysed lymphocyte count, troponin, and survival in 4874 STEMI/pPCI patients, evaluated lymphocyte kinetics during reperfusion in a prospective cohort, and obtained sequential cardiac MRI (cMRI) to assess remodeling. Pre-reperfusion lymphopenia independently predicted mortality at 7.5 years. Prior to reperfusion, CCR7+ T-lymphocytes appeared to be depleted. After reperfusion, T-lymphocytes expressing CX3CR1 were depleted predominantly in CMV-seropositive patients. During ischaemia/reperfusion, a drop in CX3CR1+ T-lymphocytes was significantly linked with microvascular obstruction in CMV+ patients, suggesting increased fractalkine-receptor interaction. At 12 weeks, CMV+ patients displayed adverse LV remodeling. We show that lymphopenia occurs before and after reperfusion in STEMI by different mechanisms and predicts long-term outcome. In CMV+ patients, increased fractalkine induction and sequestration of CX3CR1+ T-cells may contribute to adverse remodeling, suggesting a pro-inflammatory pathomechanism which presents a novel therapeutic target.
登录
查看更多内容
影响因子：
37.8
作者：
Siscovick, DS;Schwartz, SM;Kronmal, RA
通讯作者：
Kronmal, RA
影响因子：
11.3
作者：
Chia, Stanley;Senatore, Fred;Jang, Ik-Kyung
通讯作者：
Jang, Ik-Kyung
DOI：
10.1056/nejmoa1809798
发表时间：
2019-02-21
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ridker PM;Everett BM;Pradhan A;MacFadyen JG;Solomon DH;Zaharris E;Mam V;Hasan A;Rosenberg Y;Iturriaga E;Gupta M;Tsigoulis M;Verma S;Clearfield M;Libby P;Goldhaber SZ;Seagle R;Ofori C;Saklayen M;Butman S;Singh N;Le May M;Bertrand O;Johnston J;Paynter NP;Glynn RJ;CIRT Investigators
通讯作者：
CIRT Investigators
DOI：
10.2353/ajpath.2010.090759
发表时间：
2010-05
期刊：
The American journal of pathology
影响因子：
--
作者：
Dobaczewski M;Xia Y;Bujak M;Gonzalez-Quesada C;Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
6.4
作者：
Libri, Valentina;Azevedo, Rita I.;Akbar, Arne N.
通讯作者：
Akbar, Arne N.