Department of Preventive Medicine and Public Health, Keio University School of Medicine.
J Atheroscler Thromb. 2019 Sep 1;26(9):747-757. doi: 10.5551/jat.RV17036. Epub 2019 Aug 2.
Metabolomics has developed as a powerful tool for investigating the complex pathophysiology underlying atherosclerosis and cardiovascular disease. Many epidemiological studies have applied this technique to accurately and comprehensively assess the effects of environmental factors on health outcomes, which used to be a perpetual challenge. Metabolites are defined as small molecules which are intermediate products of metabolic reactions catalyzed by numerous enzymes occurring within cells. Consequent to both genetic variation and environment, they allow us to explore the gene-environment interactions and to gain a better understanding of multifactorial diseases like cardiovascular disease. This review article highlights the findings of well-known prospective cohort studies around the world that have utilized metabolomics for a wide range of purposes, including biomarker discovery, improving cardiovascular risk prediction and early disease diagnosis, and exploring detailed mechanisms of disease onset and progression. However, technical challenges still exist in applying them clinically. One limitation is due to various analytical platforms that are used based on the judgment of each study; comparative assessments among different platforms need to be conducted in order to correctly interpret and validate each data externally. Secondly, metabolite levels obtained in most high-throughput metabolomics profiling studies are often semiquantitative rather than fully quantitative concentrations, which makes it difficult to compare and combine results among different studies and to determine the levels for practical use. In 2014, the Consortium of Metabolomics Studies was developed, which is expected to take the lead in overcoming these issues.
代谢组学已发展成为研究动脉粥样硬化和心血管疾病背后复杂病理生理学的有力工具。许多流行病学研究都应用了这项技术,以准确和全面地评估环境因素对健康结果的影响,这在以前是一个永恒的挑战。代谢物被定义为小分子,是细胞内许多酶催化的代谢反应的中间产物。由于遗传变异和环境的影响,它们使我们能够探索基因-环境相互作用,并更好地理解心血管疾病等多因素疾病。本文综述了世界各地著名的前瞻性队列研究的发现,这些研究利用代谢组学来实现广泛的目的,包括生物标志物的发现、改善心血管风险预测和早期疾病诊断,以及探索疾病发病和进展的详细机制。然而,在临床应用中仍然存在技术挑战。一个限制是由于每个研究都基于判断而使用了各种分析平台;需要进行不同平台之间的比较评估,以便正确解释和验证每个外部数据。其次,在大多数高通量代谢组学分析研究中获得的代谢物水平通常是半定量的,而不是完全定量的浓度,这使得比较和结合不同研究的结果以及确定实际使用的水平变得困难。2014 年,代谢组学研究联盟成立,有望率先克服这些问题。