Secretion of prohormone of b-type natriuretic peptide, proBNP1-108: Is increased in heart failure

Lisa C. Costello-Boerrigter, Harald Lapp, Guido Boerrigter, Amir Lerman, Alexander Bufe, Fima Macheret, Denise M. Heublein, Catherine Larue, John C. Burnett

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Objectives: Using a novel, specific assay for proBNP1-108, this study tested the hypotheses that proBNP1-108 is secreted by both nonfailing and failing human hearts and that proBNP1-108 secretion is increased in failing hearts. Background: The prohormone of B-type natriuretic peptide (proBNP1-108) is a 108-amino acid peptide produced primarily by the heart and cleaved into biologically active BNP1-32 and the biologically inactive NT-proBNP1-76. It is unknown to what extent increased cardiac proBNP1-108 secretion compared to reduced peripheral processing is responsible for elevated proBNP1-108 levels in patients with heart failure (HF) compared to subjects without HF. Methods: The transcardiac gradient of proBNP1-108 was determined by collecting arterial blood and blood from the coronary sinus (CS). Samples from subjects without overt heart disease (n = 9) were collected during cardiac catheterization after coronary artery disease had been excluded. Samples from HF patients (n = 21) were collected during implantation of a biventricular pacemaker. ProBNP1-108 was measured with a new assay. Values are medians (25th/75th percentiles). Results: The gradient of proBNP1-108 across the nonfailing hearts was 8 (2/20) ng/l (aorta: 15 [1/25] ng/l; CS: 24 [8/41] ng/l; p = 0.018). The transcardiac gradient of proBNP1-108 in the failing hearts was 326 (96/482) ng/l (arterial: 381 [201/586] ng/l; CS: 709 [408/1,087] ng/l; p<0.001). The transcardiac gradient was greater in failing than nonfailing hearts (p = 0.001). Conclusions: ProBNP1-108 is secreted by nonfailing and failing human hearts, but more so in the latter. It remains to be established where peripheral processing of proBNP1-108 occurs and how this is affected by disease.

Original languageEnglish (US)
Pages (from-to)207-212
Number of pages6
JournalJACC: Heart Failure
Volume1
Issue number3
DOIs
StatePublished - Jun 1 2013

Keywords

  • Biomarker
  • Heart failure
  • Natriuretic peptides
  • ProBNP

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Costello-Boerrigter, L. C., Lapp, H., Boerrigter, G., Lerman, A., Bufe, A., Macheret, F., Heublein, D. M., Larue, C., & Burnett, J. C. (2013). Secretion of prohormone of b-type natriuretic peptide, proBNP1-108: Is increased in heart failure. JACC: Heart Failure, 1(3), 207-212. https://doi.org/10.1016/j.jchf.2013.03.001