Plasma levels and molecular forms of proatrial natriuretic peptides in healthy subjects and in patients with congestive heart failure

Abstract

A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1-30). Plasma concentrations of proANP(1-30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1-30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1-30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1-30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1-30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP.

Molecular Heterogeneity Has a Major Impact on the Measurement of Circulating N-Terminal Fragments of A- and B-Type Natriuretic Peptides

“…Our HPLC data appeared to be consistent with previous finding (25 ) indicating that NT-proANP circulates in human blood as a single peptide, NT-proANP . On the other hand, our results were clearly at odds with the previous detection of multiple defined fragments of NTproANP in human circulation (26 ).…”

“…Synthetic peptides (NT-proANP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] , NT-proANP 20 -38 , NT-proANP 26 -46 , NT-proANP 39 -59 , NT-proANP 60 -80 , NT-proANP 70 -90 , NT-proANP 88 -98 , NT-proBNP , NTproBNP 4 -16 , NT-proBNP [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] , NT-proBNP 10 -29 , NTproBNP [22][23][24][25][26][27][28]…”

“…Furthermore, there is some debate about the actual circulating forms. NTproANP has been reported to circulate in humans almost exclusively as intact NT-proANP (25 ). Alternatively, proANP has been found to be broken down into NT-proANP , NT-proANP , and NT-proANP , which have vasoactive properties (26 ).…”

Measurement and significance of circulating natriuretic peptides in cardiovascular disease

“…Although numerous studies suggest that ANP and BNP (or their precursor fragments) could be used to identify LV dysfunction, there has been considerable controversy about (i) which natriuretic peptide should actually be measured, and (ii) what is the practical value of plasma levels of these peptides in the assessment of heart disease. Regarding the first, one should keep in mind that raised plasma levels of ANP and BNP in patients with cardiovascular disease are usually also associated with higher levels of the corresponding precursors (and N-terminal segments), and thus peptide levels are strongly inter-correlated [21,22,27,34,48]. However, it is also apparent that differences in pathophysiology and\or differences in elimination rates may lead to subtle differences in the relative proportion of the plasma levels of these peptides.…”

Protease corin expression and activity in failing hearts

“…Like many peptide hormones, the natriuretic peptides are made as precursors that are converted to active forms by proteolysis. In patients with HF, plasma pro-ANP and pro-BNP levels are highly increased (1,2,5,11,20,33,42), suggesting that the processing of these peptides may be compromised under pathological conditions.Corin is a cardiac transmembrane protease that processes natriuretic peptides (38, 39). In mice, lack of corin prevented natriuretic peptide processing and caused hypertension (4).…”