King's British Heart Foundation Centre, King's College London, 125 Coldharbour Lane, London SE5 9NU, United Kingdom.
Arterioscler Thromb Vasc Biol. 2013 Feb;33(2):206-14. doi: 10.1161/ATVBAHA.112.300141.
The postgenomic shift in paradigm from reductionism to systems-wide network inference has increased recognition that cardiovascular diseases are not simply determined by the genome but arise from an interaction and dynamic dysregulation of gene regulatory networks, proteins, and metabolic alterations. The advent of postgenomic technologies promises to interrogate these complex pathophysiological perturbations by applying concepts of systemic relationships to biomarker discovery. A multibiomarker panel consisting of biomarkers capturing different levels of information (eg, microRNAs to assess endothelial and platelet activation, molecular lipid species to profile metabolic status, and proteolytic degradation products to assess vascular integrity) could outperform inflammatory biomarkers without vascular specificity in their ability of predicting cardiovascular risk. As atherosclerosis develops over decades, different biomarkers may be required for different stages of disease. Thus far, there is no simple blood test to directly assess the health of blood vessels or identify vulnerable patients. We discuss strategies for biomarker discovery using post genomics technologies, with a particular focus on circulating microRNAs. The aim is to reveal distinctive cardiovascular phenotypes and identify biomarker signatures that complement the Framingham risk scores in clinical decision-making and in a stratified medicine approach for early preventive treatment of disease.
在后基因组时代，研究范式从还原论向全系统网络推断转变，人们越来越认识到，心血管疾病不仅仅取决于基因组，而是源于基因调控网络、蛋白质和代谢改变的相互作用和动态失调。后基因组技术的出现有望通过将系统关系的概念应用于生物标志物的发现来探究这些复杂的病理生理紊乱。一个多生物标志物面板由捕获不同层次信息的生物标志物组成（例如，用于评估内皮细胞和血小板激活的 microRNAs、用于描绘代谢状态的分子脂质种类、以及用于评估血管完整性的蛋白水解降解产物），在预测心血管风险方面，其性能可能优于没有血管特异性的炎症生物标志物。由于动脉粥样硬化在几十年中发展，因此不同阶段的疾病可能需要不同的生物标志物。到目前为止，还没有一种简单的血液测试可以直接评估血管的健康状况或识别易患病人群。我们讨论了使用后基因组技术进行生物标志物发现的策略，特别关注循环 microRNAs。目的是揭示独特的心血管表型，并确定生物标志物特征，以补充 Framingham 风险评分，用于临床决策和分层医学方法，以早期预防疾病。
