The Role of Emerging Biomarkers in Unraveling the Complex Biology Underlying Associations between HDL Cholesterol and Cardiovascular Diseases

摘要

The potential for new therapies that might delay the onset of life-threatening cardiovascular events has motivated a continued interest in the identification of novel predictive circulating biomarkers for cardiovascular disease (CVD).2 While a number of biomarkers [such as C-reactive protein (CRP), d-dimer, fibrinogen, and B-type natriuretic peptide] demonstrate a strong positive association with future risk of CVD events, they have modest incremental predictive power when added to clinical risk factors (1). There remains interest in the discovery of new biomarkers of CVD risk that are uncorrelated to existing markers and provide complementary information on the biological mechanisms determining cardiovascular risk. Emerging technologies such as nuclear magnetic resonance (NMR) spectroscopy enable the comprehensive study of yet-undescribed biological territories and serve as rich ground for the discovery of new and potentially informative circulating molecules in the blood.The serum “glycome” is a fascinating example of an emerging paradigm for the discovery of new biomarkers to characterize disease risk and pathophysiology. The glycome represents the totality of posttranslational modifications of secreted proteins by enzymatic glycosylation. Glycosylated proteins and their sugar moieties called glycans are key to a variety of important cellular processes, but they have historically been difficult to measure, owing in part to low plasma concentrations. In 2015, LabCorp developed a spectral deconvolution algorithm to qualify additional signals derived from lipoprotein particle analyses originating from the N- acetyl methyl group protons of mobile glycan residues (2). This composite signal, designated “GlycA,” is thought to represent a composite of glycoproteins involved in the biology of inflammation, most prominently α1 …