MS-based approaches to unravel the molecular complexity of proprotein-derived biomarkers and support their quantification: the examples of B-type natriuretic peptide and apelin peptides.

The specific forms of described protein biomarkers that occur in human blood are not yet fully established. Even though B-type natriuretic peptide (BNP) and N-terminal proBNP are now well known markers of heart failure and other cardiac disorders, several studies yielded highly controversial results reporting various truncated, multimerized or modified forms in human blood. Similar discrepancies were observed for other biomarkers also originating from proproteins, such as the apelin peptides. The drawback of most of these studies is that they used methods with low resolving power, such as immunoassays after HPLC separation. MS-based techniques may be able to avoid such flaws. In this review, we discuss the usefulness of MS-based approaches for the characterization of circulating forms of peptide biomarkers that originate from a given proprotein. Two particular examples are discussed in detail: BNP-related peptides and some more putative biomarkers of heart failure, the apelin peptides.