Natriuretic peptides in human heart: Novel insight into their molecular forms, functions, and diagnostic use

Among the three natriuretic peptides, atrial/A-type natriuretic peptide (ANP) and brain/B-type natriuretic peptide (BNP) are primarily produced by, and secreted from, heart tissue. They maintain cardiovascular homeostasis by binding to natriuretic peptide receptor-A. Since plasma ANP and BNP concentrations, as well as expression, are elevated in response to increased body fluid volume and pressure load on the heart wall, these peptides are widely utilized as diagnostic biomarkers for evaluating heart failure. Regardless of their high utility, differences in their molecular forms between healthy and diseased subjects and how these relate to pathophysiology have not well been examined. Recent studies have shown that the circulating molecular forms of ANP and BNP are not uniform; bioactive α-ANP is the major ANP form, whereas the weakly active proBNP is the major BNP form. The relative ratios of the different molecular forms are altered under different pathophysiological conditions. These facts indicate that detailed measurements of each form may provide useful information on the pathophysiological state of heart tissue. Here, we revisit the relationship between the molecular forms of, and pathophysiological alterations in, human ANP and BNP and discuss the possible utility of the measurement of each of the molecular forms. The third peptide, C-type natriuretic peptide, activates natriuretic peptide receptor-B, but little is known about its production and function in the heart because of its extremely low levels. However, through recent studies, its role in the heart is gradually becoming clear. Here, we summarize its molecular forms, assay systems, and functions in the heart.