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.