Johny Ebin, Bhaskar Pathoori, Alam Md Jahangir, Kuladhipati Indra, Das Rupam, Adela Ramu
Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India.
Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Guwahati, Assam, 781101, India.
J Inflamm Res. 2021 Oct 7;14:5131-5147. doi: 10.2147/JIR.S326716. eCollection 2021.
Type 2 diabetes mellitus (T2DM) is a well-established risk factor for the development of atherosclerotic coronary artery disease. Platelet hyperactivity and inflammation are associated with the development of coronary artery disease (CAD) in T2DM patients. We investigated the status of immune cells, platelet activation, and platelet-immune cell interactions in T2DM_CAD patients.
The study population consisted of four groups of subjects, healthy control (CT, n = 20), T2DM (n = 44), CAD (n = 20) and T2DM_CAD (n = 38). Platelet activation, immunome profiling and platelet-immune cell interactions were analysed by flow cytometry. The circulatory levels of inflammatory cytokines/chemokines were assessed using multiplex assay.
Increased platelet activation and increased platelet-immune cell aggregate formation were observed in T2DM and T2DM_CAD groups compared to the control and CAD groups (p < 0.05). Our immunome profile analysis revealed, altered monocyte subpopulations and dendritic cell populations in T2DM, CAD and T2DM_CAD groups compared to the control group (p < 0.05). Furthermore, significantly increased IL-1β, IL-2, IL-4, IL-6, IL-8, IL12p70, IL-13 IL-18, CCL2, and decreased CXCL1, CCL5 levels were observed in T2DM_CAD group compared to the control group. Our ex-vivo study increased platelet-monocyte aggregate formation was observed upon D-glucose exposure in a time and concentration dependent manner.
Our data suggests that T2DM, CAD and T2DM_CAD are associated with altered immune cell populations. Furthermore, it has been confirmed that hyperglycemia induces platelet activation and forms platelet-immune cell aggregation which may lead to the release of inflammatory cytokines and chemokines and contribute to the complexity of CAD and type 2 diabetes.
2型糖尿病（T2DM）是动脉粥样硬化性冠状动脉疾病发生的既定危险因素。血小板高活性和炎症与T2DM患者冠状动脉疾病（CAD）的发生有关。我们研究了T2DM合并CAD患者的免疫细胞状态、血小板活化及血小板-免疫细胞相互作用。
研究人群包括四组受试者，健康对照（CT，n = 20）、T2DM（n = 44）、CAD（n = 20）和T2DM合并CAD（n = 38）。通过流式细胞术分析血小板活化、免疫组分析及血小板-免疫细胞相互作用。使用多重检测法评估循环中炎性细胞因子/趋化因子水平。
与对照组和CAD组相比，T2DM组和T2DM合并CAD组观察到血小板活化增加及血小板-免疫细胞聚集体形成增加（p < 0.05）。我们的免疫组分析显示，与对照组相比，T2DM组、CAD组和T2DM合并CAD组的单核细胞亚群和树突状细胞群体发生改变（p < 0.05）。此外，与对照组相比，T2DM合并CAD组观察到IL-1β、IL-2、IL-4、IL-6、IL-8、IL12p70、IL-13、IL-18、CCL2显著升高，CXCL1、CCL5水平降低。我们的体外研究观察到，D-葡萄糖暴露后血小板-单核细胞聚集体形成呈时间和浓度依赖性增加。
我们的数据表明，T2DM、CAD和T2DM合并CAD与免疫细胞群体改变有关。此外，已证实高血糖诱导血小板活化并形成血小板-免疫细胞聚集，这可能导致炎性细胞因子和趋化因子释放，并促使CAD和2型糖尿病病情复杂化。
