Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK.
School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.
Sci Rep. 2023 Jan 2;13(1):48. doi: 10.1038/s41598-022-26688-9.
We explored how dynamic changes in monocyte subset counts (as opposed to static values to specific time points), and their phagocytic and NFκB activity relate to major adverse cardiovascular events (MACE) and left ventricular ejection fraction (LVEF) in patients with ST-elevation myocardial infarction (STEMI). Changes in counts, phagocytic activity and intracellular levels of inhibitory κB kinase β (IKKβ) (a marker of NFκB activity) of monocyte subsets (CD14CD16CCR2 [Mon1], CD14CD16CCR2 [Mon2] and CD14CD16CCR2 [Mon3]) were measured by flow cytometry in patients with STEMI at baseline, and again after one week, two weeks, and one month. LVEF was measured by echocardiography at baseline and six months after STEMI. Baseline data included 245 patients (mean ± SD age 60 ± 12 years; 22% female), who were followed for a median of 46 (19-61) months. Multivariate Cox regression demonstrated that more prominent dynamic reduction in Mon2 by week 1 (n = 37) was independently associated with fewer MACE (HR 0.06, 95% CI 0.01-0.55, p = 0.01). Also, less prominent reduction in Mon2 at month 1 (n = 24) was independently predictive of 6-month LVEF. None of the other dynamic changes in monocyte subsets were associated with changes in survival from MACE. Neither phagocytic activity nor IKKβ were associated with survival for each monocyte subset. We showed how distinct pattern of dynamic changes in Mon2 are related to both MACE risk and recovery of cardiac contractility. Further research is needed to understand the mechanism of the monocyte effect and possibilities of their pharmacological manipulation.
我们探讨了单核细胞亚群计数的动态变化(与特定时间点的静态值相比)及其吞噬作用和 NFκB 活性如何与 ST 段抬高型心肌梗死(STEMI)患者的主要不良心血管事件(MACE)和左心室射血分数(LVEF)相关。通过流式细胞术测量 STEMI 患者基线时、一周后、两周后和一个月后单核细胞亚群(CD14CD16CCR2 [Mon1]、CD14CD16CCR2 [Mon2]和 CD14CD16CCR2 [Mon3])的计数、吞噬活性和细胞内抑制κB 激酶β(IKKβ)水平(NFκB 活性的标志物)。通过超声心动图在 STEMI 后基线和六个月时测量 LVEF。基线数据包括 245 名患者(平均年龄±标准差为 60±12 岁;22%为女性),中位随访时间为 46(19-61)个月。多变量 Cox 回归表明,第 1 周 Mon2 的动态降低更为明显(n=37)与 MACE 减少独立相关(HR 0.06,95%CI 0.01-0.55,p=0.01)。此外,第 1 个月 Mon2 减少不明显(n=24)独立预测 6 个月 LVEF。单核细胞亚群的其他动态变化均与 MACE 生存无相关性。吞噬活性和 IKKβ与每个单核细胞亚群的生存均无相关性。我们展示了 Mon2 的动态变化模式如何与 MACE 风险和心脏收缩功能恢复相关。需要进一步研究以了解单核细胞作用的机制及其药物干预的可能性。