Institute of Cardiovascular Sciences, City Hospital, University of Birmingham, Birmingham, UK.
Hull and East Yorkshire Hospitals NHS Trust, Castle Hill Hospital, Cottingham, UK.
Eur J Clin Invest. 2018 May;48(5):e12911. doi: 10.1111/eci.12911. Epub 2018 Mar 7.
Monocyte-platelet aggregates (MPAs) form when Mon1, Mon2 or Mon3 monocyte subsets adhere to platelets. They are pathophysiologically linked to coronary artery disease (CAD). However, their individual roles in the occurrence of diffuse CAD remain unknown.
Peripheral blood from 50 patients with diffuse CAD, 40 patients with focal CAD and 50 age-matched patients with normal coronary arteries was analysed by flow cytometry to quantify MPAs associated with individual monocyte subsets. Cutaneous forearm microcirculation was assessed using laser Doppler flowmetry at rest and after iontophoresis of acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation) at 100 μA for 60 seconds. Patients with CAD had repeat assessment at 6 and 12 months.
Baseline counts of MPAs with Mon2 subset (CD14++CD16+CC2+ monocytes) were significantly higher in patients with diffuse CAD compared to focal CAD (P = .001) and patients without CAD (P = .006). On multivariate regression, MPAs with Mon2 independently predicted diffuse CAD (odds ratio 1.10, 95% confidence interval 1.02-1.19, P = .01) and correlated negatively with endothelium-dependent microvascular vasodilation (r = -.37, P = .008), an association which persisted after adjustment for covariates. Longitudinal observation confirmed the persistence of an inverse relationship between MPAs with Mon2 and endothelium-dependent microvascular function.
Monocyte-platelet aggregates with Mon2 are increased in patients with diffuse CAD and therefore could represent an important contributor to accelerated coronary atherosclerotic progression by a mechanism involving microvascular endothelial dysfunction.
当 Mon1、Mon2 或 Mon3 单核细胞亚群黏附于血小板时，会形成单核细胞-血小板聚集物 (MPAs)。它们与冠状动脉疾病 (CAD) 在病理生理学上有关联。然而，它们在弥漫性 CAD 发生中的各自作用仍不清楚。
通过流式细胞术分析 50 例弥漫性 CAD 患者、40 例局灶性 CAD 患者和 50 例年龄匹配的正常冠状动脉患者的外周血，以定量与单个单核细胞亚群相关的 MPAs。在休息时以及经皮离子电渗法以 100μA 电流刺激 60 秒时，通过激光多普勒血流仪评估前臂皮肤微循环，分别刺激乙酰胆碱（内皮依赖性血管舒张）和硝普钠（内皮非依赖性血管舒张）。CAD 患者在 6 个月和 12 个月时进行重复评估。
与局灶性 CAD 患者（P =.001）和无 CAD 患者（P =.006）相比，弥漫性 CAD 患者的 Mon2 亚群（CD14++CD16+CC2+单核细胞）的 MPAs 基线计数明显更高。在多变量回归中，Mon2 的 MPAs 独立预测弥漫性 CAD（比值比 1.10，95%置信区间 1.02-1.19，P =.01），并且与内皮依赖性微血管血管舒张呈负相关（r = -.37，P =.008），这种关联在调整协变量后仍然存在。纵向观察证实了 Mon2 与内皮依赖性微血管功能之间的负相关关系仍然存在。
弥漫性 CAD 患者的 Mon2 单核细胞-血小板聚集物增加，因此，通过涉及微血管内皮功能障碍的机制，它们可能成为加速冠状动脉粥样硬化进展的重要因素。
