{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T15:32:59Z","timestamp":1790263979176,"version":"4.1.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2004,9,1]],"date-time":"2004-09-01T00:00:00Z","timestamp":1093996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Background: The N-terminal fragments of A- and B-type natriuretic peptides (NT-proANP and NT-proBNP) are powerful markers of cardiac function. The current assays require refinement with regard to standardization with native calibrators and the ability to detect the actual circulating forms.<\/jats:p><jats:p>Methods: The following peptides were prepared with recombinant methods: NT-proANP, NT-proBNP, proBNP1\u2013108, and Tyr0-proBNP77\u2013108. Fifteen peptides of 13\u201322 amino acids, spanning the sequences of NT-proANP and NT-proBNP, were prepared by solid-phase peptide synthesis. Two immunoassays for NT-proANP and four for NT-proBNP were set up, each with a different epitope specificity. The assays were applied for the measurement of NT-proANP and NT-proBNP in healthy individuals and in patients with acute myocardial infarction. The circulating molecular forms were analyzed by gel-filtration and reversed-phase HPLC.<\/jats:p><jats:p>Results: According to the HPLC analyses, circulating NT-proANP consists mainly of the full-length peptide, with some degradation at both ends. In contrast, circulating NT-proBNP is very heterogeneous. Most immunoreactive NT-proBNP is significantly smaller in size than NT-proBNP1\u201376, with truncation at both termini. The smallest fragments can be detected by assays directed at the central part of NT-proBNP only; assays directed at the ends gave 30\u201340% lower values. Despite the difference, the various assays correlated reasonably well with each other (r2 = 0.77\u20130.85). In patients with acute myocardial infarction, NT-proANP and NT-proBNP concentrations were 1.8\u20132.3 and 4.2\u20134.5 times higher than in healthy individuals. The development of heart failure further increased the concentrations.<\/jats:p><jats:p>Conclusions: Molecular heterogeneity of the circulating forms causes a serious risk of preanalytical errors in assays for NT-proBNP and, to a lesser extent, NT-proANP. The development of a sandwich assay for NT-proBNP would be especially challenging. The most robust and reliable assays use antibodies directed at the central portions of NT-proANP or NT-proBNP.<\/jats:p>","DOI":"10.1373\/clinchem.2004.032490","type":"journal-article","created":{"date-parts":[[2004,7,21]],"date-time":"2004-07-21T01:18:02Z","timestamp":1090372682000},"page":"1576-1588","source":"Crossref","is-referenced-by-count":142,"title":["Molecular Heterogeneity Has a Major Impact on the Measurement of Circulating N-Terminal Fragments of A- and B-Type Natriuretic Peptides"],"prefix":"10.1093","volume":"50","author":[{"given":"Minna","family":"Ala-Kopsala","sequence":"first","affiliation":[{"name":"Departments of Physiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarkko","family":"Magga","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Kuopio University Hospital, Kuopio, 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