CNR Institute of Clinical Physiology, 54100 Massa, Italy.
CNR Institute of Clinical Physiology, 20162 Milan, Italy.
Biomed Res Int. 2020 Jul 27;2020:8748934. doi: 10.1155/2020/8748934. eCollection 2020.
Atherosclerosis is an inflammatory disease with long-lasting activation of innate immunity and monocytes are the main blood cellular effectors. We aimed to investigate monocyte phenotype (subset fraction and marker expression) at different stages of coronary atherosclerosis in stable coronary artery disease (CAD) patients.
73 patients with chronic coronary syndrome were evaluated by CT coronary angiography (CTCA) and classified by maximal diameter stenosis of major vessels into three groups of CAD severity: CAD1 (no CAD/minimal CAD, ° = 30), CAD2 (non-obstructive CAD, ° = 21), and CAD3 (obstructive CAD, ° = 22). Flow cytometry for CD14, CD16, and CCR2 was used to quantify Mon1, Mon2, and Mon3 subsets. Expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, and CXCR4 was also measured. Adhesion molecules and cytokines were quantified by ELISA.
Total cell count and fraction of Mon2 were higher in CAD2 and CAD3 compared to CAD1. By multivariate regression analysis, Mon2 cell fraction and Mon2 expression of CX3CR1, CD18, and CD16 showed a statistically significant and independent increase, parallel to stenosis severity, from CAD1 to CAD2 and CAD3 groups. A similar trend was also present for CX3CR1 and HLA-DR expressions on total monocyte population. A less calcified plaque composition was associated to a higher Mon2 expression of CD16 and higher TNF- levels. IL-10 levels were lower at greater stenosis severity, while the IFN-/IL-10 ratio, a marker of a systemic pro-inflammatory imbalance, was directly correlated to stenosis degree and number of noncalcified plaques.
The results of this study suggest that a specific pattern of inflammation-correlated monocyte marker expression is associated to higher stenosis severity and less calcified lesions in stable CAD. The clinical trial Identifier is NCT04448691.
动脉粥样硬化是一种炎症性疾病，先天免疫会持续激活，单核细胞是主要的血液细胞效应物。我们旨在研究稳定型冠状动脉疾病（CAD）患者不同阶段冠状动脉粥样硬化时单核细胞表型（亚群分数和标志物表达）。
对 73 例慢性冠状动脉综合征患者进行 CT 冠状动脉造影（CTCA）评估，并根据大血管最大直径狭窄程度将 CAD 严重程度分为三组：CAD1（无 CAD/轻度 CAD，° = 30）、CAD2（非阻塞性 CAD，° = 21）和 CAD3（阻塞性 CAD，° = 22）。使用 CD14、CD16 和 CCR2 的流式细胞术来量化 Mon1、Mon2 和 Mon3 亚群。还测量了 CD14、CD16、CD18、CD11b、HLA-DR、CD163、CCR2、CCR5、CX3CR1 和 CXCR4 的表达。通过 ELISA 定量测定黏附分子和细胞因子。
CAD2 和 CAD3 患者的总细胞计数和 Mon2 亚群分数高于 CAD1。通过多变量回归分析，Mon2 细胞分数和 Mon2 表达的 CX3CR1、CD18 和 CD16 显示出统计学上显著且独立的增加，与狭窄严重程度平行，从 CAD1 到 CAD2 和 CAD3 组。单核细胞总数的 CX3CR1 和 HLA-DR 表达也呈现出类似的趋势。更钙化斑块组成与更高的 CD16 表达和更高的 TNF-α水平相关。随着狭窄严重程度的增加，IL-10 水平降低，而 IFN-/IL-10 比值，一种全身促炎失衡的标志物，与狭窄程度和无钙化斑块数量直接相关。
本研究结果表明，与更高的狭窄严重程度和稳定型 CAD 中更少的钙化病变相关的特定炎症相关单核细胞标志物表达模式。临床试验标识符为 NCT04448691。
