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1 Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark. Fax 45-3545-4640; e-mail JPG{at}dadlnet.dk.
Abstract
Background: Since the discovery of cardiac hormones almost 25 years ago, a vast amount of clinical research has identified the cardiac natriuretic peptides and their precursors as markers of heart failure. It even seems likely that the pro-B-type natriuretic peptide (proBNP)-derived peptides in plasma may become the most frequently measured peptides in the daily diagnosis and control of therapy. In contrast, the biochemistry of the peptides has received less attention.
Methods: Published data available on the National Library of Medicine (NLM) were used as the basis for the review.
Outcome: This review shows that the present understanding of the biochemistry of peptides is far from complete. In particular, cellular synthesis, including posttranslational precursor maturation, is poorly understood. Moreover, elimination of the precursor fragments is unknown. Elucidation of the molecular heterogeneity of proBNP products will therefore contribute to the understanding of the endocrine heart and may also have important diagnostic consequences. Above all, the different proBNP-derived peptides may not always be equal markers of the same pathophysiologic processes. A different metabolism and peripheral elimination may also impose new and peptide-specific limitations for diagnostic use.
Conclusions: It is necessary to focus more on the biology of the proBNP-derived peptides. In turn, new insight into the biochemistry could pave the way for more sensitive and disease-specific assays in the clinical setting.
The following articles in journals at HighWire Press have cited this article:
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  E. E. Niederkofler, U. A. Kiernan, J. O'Rear, S. Menon, S. Saghir, A. A. Protter, R. W. Nelson, and U. Schellenberger Detection of Endogenous B-Type Natriuretic Peptide at Very Low Concentrations in Patients With Heart Failure Circ Heart Fail, November 1, 2008; 1(4): 258 - 264. [Abstract] [Full Text] [PDF]
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 J. P. Goetze, U. Dahlstrom, J. F. Rehfeld, and U. Alehagen Impact of Epitope Specificity and Precursor Maturation in Pro-B-Type Natriuretic Peptide Measurement Clin. Chem., November 1, 2008; 54(11): 1780 - 1787. [Abstract] [Full Text] [PDF]
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 M. A. Roberts, P. M. Srivastava, N. Macmillan, D. L. Hare, S. Ratnaike, K. Sikaris, and F. L. Ierino B-type Natriuretic Peptides Strongly Predict Mortality in Patients Who Are Treated with Long-Term Dialysis Clin. J. Am. Soc. Nephrol., July 1, 2008; 3(4): 1057 - 1065. [Abstract] [Full Text] [PDF]
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 S. W. Waldo, J. Beede, S. Isakson, S. Villard-Saussine, J. Fareh, P. Clopton, R. L. Fitzgerald, and A. S. Maisel Pro-B-Type Natriuretic Peptide Levels in Acute Decompensated Heart Failure J. Am. Coll. Cardiol., May 13, 2008; 51(19): 1874 - 1882. [Abstract] [Full Text] [PDF]
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A. M. Hawkridge, D. C. Muddiman, D. M. Hebulein, A. Cataliotti, and J. C. Burnett Jr. Effect of Plasma Protein Depletion on BNP-32 Recovery Clin. Chem., May 1, 2008; 54(5): 933 - 934. [Full Text] [PDF]
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 M. Damgaard, J. P. Goetze, P. Norsk, and N. Gadsboll Altered sodium intake affects plasma concentrations of BNP but not proBNP in healthy individuals and patients with compensated heart failure Eur. Heart J., November 2, 2007; 28(22): 2726 - 2731. [Abstract] [Full Text] [PDF]
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C. Christoffersen, I. Hunter, A. L. Jensen, and J. P. Goetze Diabetes and the endocrine heart Eur. Heart J., October 2, 2007; 28(20): 2427 - 2429. [Full Text] [PDF]
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C. S.P. Lam, J. C. Burnett Jr, L. Costello-Boerrigter, R. J. Rodeheffer, and M. M. Redfield Alternate Circulating Pro-B-Type Natriuretic Peptide and B-Type Natriuretic Peptide Forms in the General Population J. Am. Coll. Cardiol., March 20, 2007; 49(11): 1193 - 1202. [Abstract] [Full Text] [PDF]
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F. Liang, J. O'Rear, U. Schellenberger, L. Tai, M. Lasecki, G. F. Schreiner, F. S. Apple, A. S. Maisel, N. S. Pollitt, and A. A. Protter Evidence for Functional Heterogeneity of Circulating B-Type Natriuretic Peptide J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1071 - 1078. [Abstract] [Full Text] [PDF]
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T. Borglum, J. F. Rehfeld, L. B. Drivsholm, and L. Hilsted Processing-Independent Quantitation of Chromogranin A in Plasma from Patients with Neuroendocrine Tumors and Small-Cell Lung Carcinomas Clin. Chem., March 1, 2007; 53(3): 438 - 446. [Abstract] [Full Text] [PDF]
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J. P. Goetze, R. Mogelvang, L. Maage, H. Scharling, P. Schnohr, P. Sogaard, J. F. Rehfeld, and J. S. Jensen Plasma pro-B-type natriuretic peptide in the general population: screening for left ventricular hypertrophy and systolic dysfunction Eur. Heart J., December 2, 2006; 27(24): 3004 - 3010. [Abstract] [Full Text] [PDF]
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J. P. Goetze, L. Friis-Hansen, J. F. Rehfeld, B. Nilsson, and J. H. Svendsen Atrial secretion of B-type natriuretic peptide Eur. Heart J., July 2, 2006; 27(14): 1648 - 1650. [Abstract] [Full Text] [PDF]
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J. V. St. Peter, G. G. Hartley, M. M. Murakami, and F. S. Apple B-Type Natriuretic Peptide (BNP) and N-Terminal Pro-BNP in Obese Patients without Heart Failure: Relationship to Body Mass Index and Gastric Bypass Surgery Clin. Chem., April 1, 2006; 52(4): 680 - 685. [Abstract] [Full Text] [PDF]
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A. Nohria and M. M. Givertz B-Type Natriuretic Peptide and the Stressed Heart J. Am. Coll. Cardiol., February 21, 2006; 47(4): 749 - 751. [Full Text] [PDF]
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 A. Clerico, F. A. Recchia, C. Passino, and M. Emdin Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H17 - H29. [Abstract] [Full Text] [PDF]
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I. Brandt, A.-M. Lambeir, J.-M. Ketelslegers, M. Vanderheyden, S. Scharpe, and I. De Meester Dipeptidyl-Peptidase IV Converts Intact B-Type Natriuretic Peptide into Its des-SerPro Form Clin. Chem., January 1, 2006; 52(1): 82 - 87. [Abstract] [Full Text] [PDF]
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K. G. Halse, M. L.S. Lindegaard, J. P. Goetze, P. Damm, E. R. Mathiesen, and L. B. Nielsen Increased Plasma Pro-B-Type Natriuretic Peptide in Infants of Women with Type 1 Diabetes Clin. Chem., December 1, 2005; 51(12): 2296 - 2302. [Abstract] [Full Text] [PDF]
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 A. M. Hawkridge, D. M. Heublein, H. R. Bergen III, A. Cataliotti, J. C. Burnett Jr., and D. C. Muddiman Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure PNAS, November 29, 2005; 102(48): 17442 - 17447. [Abstract] [Full Text] [PDF]
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D. L. Crimmins Human N-Terminal proBNP Is a Monomer Clin. Chem., June 1, 2005; 51(6): 1035 - 1038. [Full Text] [PDF]
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J. P. Goetze and R. Videbaek More hormones spilt in heart failure: linking renal sympathetic activation to clinical outcome Eur. Heart J., May 1, 2005; 26(9): 861 - 862. [Full Text] [PDF]
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A. Clerico, M. Emdin, J. P. Goetze, and J. F. Rehfeld Endocrine Paradox in Heart Failure: Resistance to Biological Effects of Cardiac Natriuretic Hormones * Drs. Goetze and Rehfeld respond: Clin. Chem., December 1, 2004; 50(12): 2465 - 2468. [Full Text] [PDF]
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