Laboratory of Experimental Cardiology, UMC Utrecht, Room G02.523, Heidelberglaan 100, 3584, Utrecht, CX, The Netherlands,
Clin Res Cardiol. 2013 Nov;102(11):847-56. doi: 10.1007/s00392-013-0607-9. Epub 2013 Aug 23.
Biomarkers for primary or secondary risk prediction of cardiovascular disease (CVD) are urgently needed to improve individual treatment and clinical trial design. The vast majority of biomarker discovery studies has concentrated on plasma/serum as an easily accessible source. Although numerous markers have been identified, their added predictive value on top of traditional risk factors has been limited, as the biological specimen does not specifically reflect expression profiles related with CVD progression and because the signal is often diluted by marker release from other organs. In contrast to serum markers, circulating cells serve as indicators of the actual disease state due to their active role in the pathogenesis of CVD and are responsible for the majority of secreted biomarkers. Therefore, the CIRCULATING CELLS study was initiated, focusing on the cellular effectors of atherosclerosis in the circulation. In total, 714 patients with coronary artery disease (CAD) symptoms were included. Blood cell fractions (monocytes, T-lymphocytes, platelets, granulocytes, PBMC) of all individual patients were isolated and stored for analysis. Concomitantly, extensive flow cytometric characterization of these populations was performed. From each patient, a detailed clinical profile together with extensive questionnaires about medical history and life style was obtained. Various high-throughput -omics approaches (protein, mRNA, miRNA) are currently being undertaken. Data will be integrated with advanced bioinformatics for discovery and validation of secondary risk markers for adverse events. Overall, the CIRCULATING CELLS study grants the interesting possibility that it will both identify novel biomarkers and provide useful insights into the pathophysiology of CAD in patients.
生物标志物对于心血管疾病（CVD）的一级或二级风险预测至关重要，这有助于改善个体治疗和临床试验设计。绝大多数生物标志物发现研究都集中在血浆/血清作为一种易于获取的来源。尽管已经确定了许多标志物，但它们在传统危险因素基础上的附加预测价值有限，因为生物样本并不能特别反映与 CVD 进展相关的表达谱，而且由于标志物从其他器官释放，信号经常被稀释。与血清标志物相比，由于其在 CVD 发病机制中的积极作用，循环细胞作为疾病实际状态的指标，负责大多数分泌的生物标志物。因此，启动了 CIRCULATING CELLS 研究，重点研究循环系统中动脉粥样硬化的细胞效应物。共有 714 名有冠心病（CAD）症状的患者被纳入该研究。所有患者的血细胞分数（单核细胞、T 淋巴细胞、血小板、粒细胞、PBMC）均被分离并储存用于分析。同时，对这些细胞群进行了广泛的流式细胞术特征分析。从每位患者获得详细的临床概况，以及关于病史和生活方式的广泛问卷调查。目前正在采用各种高通量组学方法（蛋白质、mRNA、miRNA）。将数据与先进的生物信息学进行整合，以发现和验证不良事件的二级风险标志物。总体而言，CIRCULATING CELLS 研究提供了一个有趣的可能性，它将既能发现新的生物标志物，又能深入了解患者 CAD 的病理生理学。
