Ardigo Diego, Gaillard Carlo A J M, Braam Branko
Department of Internal Medicine and Biomedical Sciences, University of Parma, Italy.
Clin Chem Lab Med. 2007;45(9):1109-20. doi: 10.1515/CCLM.2007.261.
Prevention of cardiovascular disease (CVD) remains a major health issue in the Western world. The diagnostic and therapeutic approach is currently based on risk factor assessment and treatment, which adequately predicts CVD at population level, but not at the level of a single individual. This may arise from the fact that the stage and activity of complex disease states are not likely to be captured by a single parameter or a small set of markers and thus may need a more complex representation. The aim of this review is to explore the possibility of pursuing the use of high-throughput gene expression profiling as a way to improve diagnosis, prognosis and monitoring of the disease. Novel chip-based techniques such as oligo- and cDNA microarrays can measure the abundance of thousands of mRNA transcripts in parallel and thus provide a comprehensive picture of the cell phenotype. Circulating white blood cells (WBCs), which are exposed to the systemic environment (including the risk factors) and are directly involved in the low-grade chronic inflammation related to CVD, have the potential to be used in this context to improve phenotyping of the patient. The paper reviews conceptual limitations in the use of risk factors and biomarkers, and shows the rationale beyond the possible use of circulating WBCs or subpopulations as representative cells to monitor systemic consequences of CVD. Methodological issues in performing microarray analysis of WBCs are also addressed, including controversies related to the choice of adequate cell populations and reference samples. Reproducibility and challenges occurring in the definition of a disease-specific gene panel are also discussed. The available proofs of principle from the literature presented in the last section of the review further support exploration of the application of circulating cell transcriptomics in CVD.
在西方世界，心血管疾病（CVD）的预防仍然是一个重大的健康问题。目前的诊断和治疗方法基于风险因素评估和治疗，这在人群层面能够充分预测心血管疾病，但在个体层面却并非如此。这可能是因为复杂疾病状态的阶段和活动不太可能通过单一参数或一小套标志物来反映，因此可能需要更复杂的表征方式。本综述的目的是探讨采用高通量基因表达谱分析来改善该疾病诊断、预后和监测的可能性。基于芯片的新技术，如寡核苷酸和cDNA微阵列，能够并行测量数千种mRNA转录本的丰度，从而提供细胞表型的全面图景。循环白细胞（WBC）暴露于全身环境（包括风险因素），并直接参与与心血管疾病相关的低度慢性炎症，因此有潜力在这种情况下用于改善患者的表型分析。本文回顾了风险因素和生物标志物使用中的概念性局限性，并阐述了将循环白细胞或亚群作为代表性细胞来监测心血管疾病全身影响的潜在理由。还讨论了对白细胞进行微阵列分析时的方法学问题，包括与选择合适细胞群体和参考样本相关的争议。同时也探讨了在定义疾病特异性基因面板时出现的可重复性和挑战。综述最后一部分呈现的文献中的现有原理证明进一步支持了对循环细胞转录组学在心血管疾病中应用的探索。
