3.2.2 Novel diagnostic strategies of BSMs-based biomarkers in CVD
At the same time, with the development of detection technology, the clinical application of BSMs in cardiovascular diseases has gradually been widened. Many BSMs in human fluids can also be detected as biomarkers for various cardiovascular diseases.
Pathogenesis and diagnostic biomarkers for diseases can be discovered by metabolomic profiling of human fluids. If the various types of coronary artery disease (CAD) can be accurately characterized by metabolomics, effective treatment may be targeted without using unnecessary therapies and resources. Metabolic disorder is a characteristic of CAD, but there is lack of clinical detection of patient metabolism. A study was conducted to characterize metabolic imbalance by plasma BSMs in different types of CAD [107]. Differential metabolic small molecules including bile acids, amino acids, short chain acylcarnitines, tricarboxylic acid (TCA) cycle metabolites and phospholipids were shown to change in different CAD stages. By function enrichment and cluster analysis, these metabolic BSMs were indicated to alter different metabolic pathways. At the same time, 12 panels of specific metabolomics-based biomarkers were tested in the multicenter trial and highlighted a high sensitivity and specificity of diagnosing CAD at different stages. This showed the great potential clinical application of BSMs as biomarkers in cardiovascular disease.
Further, with the help of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode, a small molecule biomarker N-acetylneuraminic acid (Neu5Ac) was identified to increase in patient plasma and shown a potential role in the pathological progression of CAD [108]. And the regulation network of this small molecule was associated with myocardial injury. By activating the Rho/Rho-associated coiled-coil containing protein kinase signaling pathway, Neu5Ac triggered RhoA and Cdc42-dependent myocardial injury. What’s more, it was found that myocardial ischemia injury could be ameliorated after silencing neuraminidase-1, the regulatory enzyme of Neu5Ac, which served as a novel potential drug target for CAD treatment.