Department of Cardiology, Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Madrid, Spain.
J Am Coll Cardiol. 2010 May 11;55(19):2009-16. doi: 10.1016/j.jacc.2010.01.036.
Extensive research has focused on the identification of novel plasma biomarkers to improve our ability to predict cardiovascular events in atherothrombosis. However, classical techniques can only assess a limited number of proteins at a time. Given that plasma contains more than 900,000 proteins, this approach will be extremely time-consuming. Novel proteomic approaches make it possible to compare the expression of hundreds of proteins in several samples in a single experiment. The classical approach consists of separation of proteins on a 2-dimensional gel followed by protein identification with mass spectrometry, although new complementary gel-free techniques are emerging. We can thus compare protein expression in an atherosclerotic plaque with that in a normal artery or study plasma proteins in patients with atherothrombosis as compared with healthy subjects. For such approaches, it is not necessary to study the published data to select potential biomarkers. However, because the number of patients that can be studied with most of these techniques is limited, what is really important is the design of the studies, assessing carefully what kind of patients should be included to obtain valid conclusions. Clinicians should thus play a key role in this design along with the basic scientist. In this article, we review several proteomic strategies carried out by our group and others, and we make a call for collaboration between clinicians and experts in proteomics. This collaboration could greatly increase the likelihood of identifying new prognostic biomarker panels in atherothrombosis and other cardiovascular disorders.
已经有大量研究致力于寻找新的血浆生物标志物,以提高我们预测动脉粥样硬化血栓形成性心血管事件的能力。然而,传统技术一次只能评估有限数量的蛋白质。鉴于血浆中含有超过 900000 种蛋白质,这种方法将极其耗时。新型蛋白质组学方法使得在单个实验中比较数百种蛋白质在几个样本中的表达成为可能。经典方法包括在二维凝胶上分离蛋白质,然后用质谱法进行蛋白质鉴定,尽管新的互补无胶技术正在出现。因此,我们可以比较动脉粥样硬化斑块中的蛋白质表达与正常动脉中的蛋白质表达,或者研究动脉粥样硬化血栓形成患者的血浆蛋白质与健康受试者的蛋白质表达。对于这些方法,不必研究已发表的数据来选择潜在的生物标志物。然而,由于大多数这些技术所能研究的患者数量有限,真正重要的是研究设计,仔细评估应该纳入什么样的患者才能得出有效的结论。因此,临床医生应该与基础科学家一起在这一设计中发挥关键作用。在本文中,我们回顾了我们小组和其他小组进行的几种蛋白质组学策略,并呼吁临床医生和蛋白质组学专家之间开展合作。这种合作极有可能在动脉粥样硬化血栓形成和其他心血管疾病中识别出新的预后生物标志物组合。