Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India.
Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, Guwahati, Assam, India; Pittsburgh Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh, PA, USA.
Cytokine. 2024 Jun;178:156581. doi: 10.1016/j.cyto.2024.156581. Epub 2024 Mar 19.
The development of coronary artery disease (CAD) depends heavily on platelet activation, and inflammation plays a major role in all stages of atherosclerosis. Platelet-specific soluble triggering receptor expressed on myeloid cells like transcript 1 (sTLT-1) facilitate clot formation and have been linked to chronic inflammation. In this study, we explored the role of platelet-derived sTLT-1 in platelet-mediated inflammation in CAD patients. Plasma levels of sTLT-1 were measured using enzyme-linked immunosorbent assay in CAD patients (n = 163) and healthy controls (n = 99). Correlation analysis was performed to determine the circulatory sTLT-1 levels with platelet activation markers, immune cells, and inflammatory cytokines/chemokines. Increased plasma sTLT-1 levels were observed in CAD patients compared with those in healthy controls (p < 0.0001). A positive correlation was observed between sTLT-1 and platelet activation markers (P-selectin, PAC-1), CD14++ CD16- cells (classical monocytes), Natural killer T (NKT) cells, and platelet-immune cell aggregates with monocytes, neutrophils, dendritic cells, CD11c+ cells, and NKT cells. In contrast, a significant negative correlation was observed with CD8 cells. Furthermore, a significant positive correlation was observed between sTLT-1 and inflammatory markers (TNF-α, IL-1β, IL-2, IL-6, IL-12p70, IL-18, CXCL-12, and CCL-11). Logistic regression analysis identified sTLT-1 and triglycerides as predictors of CAD. Receiver operating characteristic curve (ROC) analysis showed that sTLT-1 had a higher sensitivity and specificity for predicting CAD. Our findings suggest that platelet activation induces the release of sTLT-1 into the circulation in CAD patients, which aggregates with immune cells and enhances inflammatory responses.
冠心病（CAD）的发展在很大程度上依赖于血小板的激活，炎症在动脉粥样硬化的所有阶段都起着主要作用。血小板特异性可溶性髓样细胞触发受体表达 1（sTLT-1）促进血栓形成，并与慢性炎症有关。在这项研究中，我们探讨了血小板衍生的 sTLT-1 在 CAD 患者血小板介导的炎症中的作用。使用酶联免疫吸附试验（ELISA）测量 CAD 患者（n=163）和健康对照者（n=99）的血浆 sTLT-1 水平。进行了相关分析，以确定循环 sTLT-1 水平与血小板活化标志物、免疫细胞和炎症细胞因子/趋化因子之间的关系。与健康对照组相比，CAD 患者的血浆 sTLT-1 水平升高（p<0.0001）。sTLT-1 与血小板活化标志物（P-选择素、PAC-1）、CD14++ CD16-细胞（经典单核细胞）、自然杀伤 T（NKT）细胞以及与单核细胞、中性粒细胞、树突状细胞、CD11c+细胞和 NKT 细胞的血小板-免疫细胞聚集体呈正相关。相反，与 CD8 细胞呈显著负相关。此外，sTLT-1 与炎症标志物（TNF-α、IL-1β、IL-2、IL-6、IL-12p70、IL-18、CXCL-12 和 CCL-11）之间呈显著正相关。逻辑回归分析确定 sTLT-1 和甘油三酯是 CAD 的预测因子。受试者工作特征曲线（ROC）分析显示，sTLT-1 对预测 CAD 的敏感性和特异性更高。我们的研究结果表明，在 CAD 患者中，血小板激活诱导 sTLT-1 释放到循环中，与免疫细胞聚集并增强炎症反应。
