Secretion of Prohormone of B-Type Natriuretic Peptide, proBNP1-108, Is Increased in Heart Failure
Author + information
- Lisa C. Costello-Boerrigter, MD, PhD∗∗ (costello.boerrigter{at}gmail.com),
- Harald Lapp, MD†,‡,
- Guido Boerrigter, MD∗,
- Amir Lerman, MD∗,
- Alexander Bufe, MD§,
- Fima Macheret, MD, MS∗,
- Denise M. Heublein, CLT∗,
- Catherine Larue, PhD‖ and
- John C. Burnett Jr., MD∗
- ↵∗Reprint requests and correspondence:
Dr. Lisa C. Costello-Boerrigter, Cardiorenal Research Laboratory, Mayo Clinic and Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905.
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.
Footnotes
This work was supported by National Institutes of Health grants HL36634 (to Drs. Costello-Boerrigter, Boerrigter, and Burnett) and HL76611. Dr. Larue was an employee of Bio-Rad. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received September 19, 2012.
- Revision received March 4, 2013.
- Accepted March 5, 2013.
- American College of Cardiology Foundation
