Mass Spectrometry Application in Atherosclerosis (AS) Biomarkers Detection

Atherosclerosis (AS) is caused by fatty deposits, also called cholesterol accumulation in the arteries. The deposits mainly consist of cholesterol, fatty substances, calcium, and fibrin. Atherosclerosis is considered the major cause of cardiovascular diseases mainly involving the heart and brain: coronary arterial disease and ischemic stroke. It is the leading cause of death worldwide, inducing a severe financial burden in the world. The causes of AS include unmodifiable and modifiable risk factors. Modifiable risk factors include hypercholesterolemia, hypertension, biomarkers of cholesterol, and angiotensin which can be used in the clinic for the assessment of AS process. Mass spectrometry is a promising tool for the interrogation of AS biomarkers through analyzing lipids and metabolites during the disease process, however, it is hampered by the laborious steps, and time-consuming sampling process. Paper-loaded direct analysis in real-time (pDART)-MS can be used to detect cholesterol in serum to realize simple sample preparation and accurate detection of cholesterol when compared with fluorometric-enzymatic (FL) commercial assays¹. The pathology of AS is complicated, and the unmet need for new biomarkers discovery to improve the risk assessment for AS is needed². Probe electrospray ionization (PESI)-MS is an ambient ionization technique that was used for the new biomarkers discovery in rabbit plasma and accurately discriminated the rabbit with or without dyslipidemia due to genetic or environment cause³ and discovery of a potential biomarker of AS without tedious sampling process. In the clinical setting, radioimmunoassays (IRAs) is used for hypertension monitoring, but it is hindered by using radioactive isotopes, low limit of detection (LOD), and long incubation time. Immuno-matrix-assisted laser desorption ionization (iMALDI)-MS achieved sensitivity and specificity detection of angiotensin I in human plasma showing a wider detection range and shorter incubation time when compared with the IRAs⁴. 

References 

1. Hsieh, H.-Y.;  Li, L.-H.;  Hsu, R.-Y.; Kao, W.-F.;  Huang, Y.-C.; Hsu, C.-C., Quantification of Endogenous Cholesterol in Human Serum on Paper Using Direct Analysis in Real Time Mass Spectrometry. Analytical Chemistry 2017,89 (11), 6146-6152.
2. Hoefer, I. E.;  Steffens, S.; Ala-Korpela, M.;  Bäck, M.;  Badimon, L.; Bochaton-Piallat, M.-L.; Boulanger, C. M.;  Caligiuri, G.;  Dimmeler, S.;  Egido, J.; Evans, P. C.;  Guzik, T.;  Kwak, B. R.; Landmesser, U.;  Mayr, M.;  Monaco, C.; Pasterkamp, G.;  Tuñón, J.;  Weber, C.; the, E. S. C. W. G. A.; Vascular, B., Novel methodologies for biomarker discovery in atherosclerosis. European Heart Journal 2015, 36 (39), 2635-2642.
3. Johno, H.;  Yoshimura, K.;  Mori, Y.; Kimura, T.;  Niimi, M.;  Yamada, M.; Tanigawa, T.;  Fan, J.; Takeda, S., Detection of potential new biomarkers of atherosclerosis by probe electrospray ionization mass spectrometry. Metabolomics 2018, 14 (4), 38.
4. Reid, J. D.;  Holmes, D. T.;  Mason, D. R.; Shah, B.; Borchers, C. H., Towards the development of an immuno MALDI (iMALDI) mass spectrometry assay for the diagnosis of hypertension. Journal of the American Society for Mass Spectrometry 2010, 21 (10), 1680-1686.