FCGR2A-HH Gene Variants Encoding the Fc Gamma Receptor for the C-Reactive Protein Are Associated with Enhanced Monocyte CD32 Expression and Cardiovascular Events' Recurrence after Primary Acute Coronary Syndrome.
FCGR2A-HH Gene Variants Encoding the Fc Gamma Receptor for the C-Reactive Protein Are Associated with Enhanced Monocyte CD32 Expression and Cardiovascular Events' Recurrence after Primary Acute Coronary Syndrome.
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DOI：
10.3390/biomedicines10020495
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发表时间：
2022-02-19
期刊：
影响因子：
4.7
通讯作者：
Bonello L
中科院分区：
文献类型：
--
作者：
Paul P;Picard C;Lyonnet L;Resseguier N;Hubert L;Arnaud L;Di Cristofaro J;Laine M;Paganelli F;Dignat-George F;Frère C;Sabatier F;Guieu R;Bonello L
Fcγ 受体 (FcγR) 与 C 反应蛋白 (CRP) 相互作用，介导激活影响心血管健康的炎症相关致病机制。我们的研究评估了 FcγRIIA 和 FcγRIIIA 谱是否与原发性急性冠脉综合征 (ACS) 后第一年内不良心血管事件的复发相关。主要终点是心血管事件（RCE）的复发，被确定为包括急性心力衰竭（AHF）和主要不良心血管事件（MACE）的复合结局。我们获取了 145 名 ACS 患者的血液样本，以测量 hsCRP 循环水平，鉴定 FcγRIIA-131RH rs1801274 和 FcγRIIIA-158FV rs396991 多态性，分析表达 CD16 和 CD32 的循环单核细胞和 NK 细胞亚群，并通过荧光素酶报告基因测定检测血清介导的 FCGR2A-HH 激活。所有患者的 hsCRP、CD32 表达和 Fc-R 介导的激活水平相似，无论其 MACE 风险如何。相比之下，发生 AHF 的患者的 hsCRP 水平和表达 CRP CD32 受体的 CD14+ 循环单核细胞的比例显着较高。 FCGR2A rs1801274 HH 基因型在发生 RCE 和 MACE 的患者中比无 RCE 的患者更常见，并且与循环 CD32+CD14+ 单核细胞百分比增加相关。通过多变量分析，FCGR2A-HH 基因型被确定为后续 RCE 的独立预测因子（OR，2.7；p = 0.048；CI，1.01-7.44）。这些发现提供了初步证据，表明宿主 FCGR2A 遗传变异可以影响单核细胞 CD32 受体表达，并可能有助于微调 CD32 驱动的慢性激活信号，从而影响原发性 ACS 事件后发生 RCE 的风险。
Fcγ receptors (FcγRs) interact with the C-reactive protein (CRP) and mediate activation of inflammation-related pathogenic mechanisms affecting cardiovascular health. Our study evaluated whether FcγRIIA and FcγRIIIA profiles are associated with the recurrence of adverse cardiovascular events during the first year after a primary acute coronary syndrome (ACS). The primary endpoint was the recurrence of cardiovascular events (RCE), identified as a composite outcome comprising acute heart failure (AHF) and major adverse cardiovascular events (MACE). We obtained blood samples of 145 ACS patients to measure hsCRP circulating levels, to identify FcγRIIA-131RH rs1801274 and FcγRIIIA-158FV rs396991 polymorphisms, to analyze circulating monocytes and NK cell subsets expressing CD16 and CD32, and to detect serum-mediated FCGR2A-HH activation by luciferase reporter assays. The hsCRP, CD32-expression, and Fc-R mediated activation levels were similar in all patients regardless of their MACE risk. In contrast, the hsCRP levels and the proportion of CD14+ circulating monocytes expressing the CD32 receptor for CRP were significantly higher in the patients who developed AHF. The FCGR2A rs1801274 HH genotype was significantly more common in patients who developed RCE and MACE than in RCE-free patients and associated with an enhanced percentage of circulating CD32+CD14+ monocytes. The FCGR2A-HH genotype was identified as an independent predictor of subsequent RCE (OR, 2.7; p = 0.048; CI, 1.01–7.44) by multivariate analysis. These findings bring preliminary evidence that host FCGR2A genetic variants can influence monocyte CD32 receptor expression and may contribute to the fine-tuning of CD32-driven chronic activating signals that affect the risk of developing RCEs following primary ACS events.
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影响因子：
24
作者：
Lindholm, Daniel;James, Stefan K.;Wallentin, Lars
通讯作者：
Wallentin, Lars
影响因子：
9.3
作者：
Devaraj, Sridevi;Kumaresan, Pappanaicken R.;Jialal, Ishwarlal
通讯作者：
Jialal, Ishwarlal
影响因子：
5.4
作者：
Carrero, Juan Jesus;Franko, Mikael Andersson;Jernberg, Tomas
通讯作者：
Jernberg, Tomas
影响因子：
5.5
作者：
Montecucco, Fabrizio;Steffens, Sabine;Mach, Francois
通讯作者：
Mach, Francois
影响因子：
15.9
作者：
PARREN, PWHI;WARMERDAM, PAM;VANDEWINKEL, JGJ
通讯作者：
VANDEWINKEL, JGJ