Recent advances in cardiovascular disease research driven by metabolomics technologies in the context of systems biology

Abstract

Traditional risk factors and biomarkers of cardiovascular diseases (CVD) have been mainly discovered through clinical observations. Nevertheless, there is still a gap in knowledge in more sophisticated CVD risk factor stratification and more reliable treatment outcome prediction, highlighting the need for a more comprehensive understanding of disease mechanisms at the molecular level. This need has been addressed by integrating information derived from multiomics studies, which provides systematic insights into the different layers of the central dogma in molecular biology. With the advancement of technologies such as NMR and UPLC-MS, metabolomics have become a powerhouse in pharmaceutical and clinical research for high-throughput, robust, quantitative characterisation of metabolic profiles in various types of biospecimens. In this review, we highlight the versatile value of metabolomics spanning from targeted and untargeted identification of novel biomarkers and biochemical pathways, to tracing drug pharmacokinetics and drug-drug interactions for more personalised medication in CVD research (Fig. 1).

Fig. 1

Summary of molecular mechanisms that can lead to cardiovascular diseases (CVD) development and how application of targeted and untargeted metabolomics approaches can help achieve more effective and personalised treatment and prevention by providing a more thorough understanding in various aspects.

Fig. 2. Patient-centric and intervention-centric metabolomics studies in CVD research.

Patient-centric studies focus on the internal changes of the subject by characterising metabolic features of biospecimens (e.g. blood, urine, faeces) using LC-MS, the goal of which are commonly to identify clinically applicable CVD biomarkers and relevant metabolic pathways, together with other omics technologies. Intervention-centric studies focus on what a subject is exposed to that leads to the development or treatment of CVD. Depending on the nature of the intervention (e.g. environmental toxins, drugs, diet), the goal of the study can be identification of specific molecular risk factors, or tracing the metabolic fates of molecules that are beneficial or harmful for CVD prevention and treatment. Figure created with BioRender.com.