Shen Xiaomeng, Young Rebeccah, Canty John M, Qu Jun
Department of Biochemistry, University at Buffalo, Buffalo, NY, USA; New York State Center of Excellence in Bioinformatics and Life Sciences, University at Buffalo, Buffalo, NY, USA.
Proteomics Clin Appl. 2014 Aug;8(7-8):488-505. doi: 10.1002/prca.201400014. Epub 2014 Jul 14.
Extensive technical advances in the past decade have substantially expanded quantitative proteomics in cardiovascular research. This has great promise for elucidating the mechanisms of cardiovascular diseases and the discovery of cardiac biomarkers used for diagnosis and treatment evaluation. Global and targeted proteomics are the two major avenues of quantitative proteomics. While global approaches enable unbiased discovery of altered proteins via relative quantification at the proteome level, targeted techniques provide higher sensitivity and accuracy, and are capable of multiplexed absolute quantification in numerous clinical/biological samples. While promising, technical challenges need to be overcome to enable full utilization of these techniques in cardiovascular medicine. Here, we discuss recent advances in quantitative proteomics and summarize applications in cardiovascular research with an emphasis on biomarker discovery and elucidating molecular mechanisms of disease. We propose the integration of global and targeted strategies as a high-throughput pipeline for cardiovascular proteomics. Targeted approaches enable rapid, extensive validation of biomarker candidates discovered by global proteomics. These approaches provide a promising alternative to immunoassays and other low-throughput means currently used for limited validation.
在过去十年中,广泛的技术进步极大地扩展了心血管研究中的定量蛋白质组学。这对于阐明心血管疾病的机制以及发现用于诊断和治疗评估的心脏生物标志物具有巨大的前景。全局蛋白质组学和靶向蛋白质组学是定量蛋白质组学的两个主要途径。虽然全局方法能够通过蛋白质组水平的相对定量无偏地发现变化的蛋白质,但靶向技术具有更高的灵敏度和准确性,并且能够在众多临床/生物样本中进行多重绝对定量。尽管前景广阔,但要在心血管医学中充分利用这些技术,仍需克服技术挑战。在此,我们讨论定量蛋白质组学的最新进展,并总结其在心血管研究中的应用,重点是生物标志物的发现和疾病分子机制的阐明。我们建议将全局和靶向策略整合为心血管蛋白质组学的高通量流程。靶向方法能够快速、广泛地验证通过全局蛋白质组学发现的生物标志物候选物。这些方法为免疫测定和目前用于有限验证的其他低通量方法提供了一种有前景的替代方案。