Diversity of molecular forms of plasma brain natriuretic peptide in heart failure--different proBNP-108 to BNP-32 ratios in atrial and ventricular overload.
OBJECTIVE
Recent studies have shown that plasma levels of brain natriuretic peptide (BNP)-32 and proBNP-108 are increased in heart failure (HF) and that the BNP-32 assay kit in current clinical use cross-reacts with proBNP-108. We investigated why proBNP is increased without processing in HF was investigated.


METHODS
Plasma BNP-32 and proBNP-108 in normal individuals (n=10) and in patients with atrial fibrillation (AF) (n=18) and HF (n=132) was measured. BNP-32 and proBNP-108 in ventricular and atrial tissue and in pericardial fluid using a specific fluorescent enzyme immunoassay following Sep-Pak C18 (Waters, Milford, Massachusetts, USA) cartridge extraction and gel filtration was also measured.


METHODS
Levels of both BNP-32 and proBNP-108 were higher in HF than in control or AF (both p<0.01), and the levels of these peptides significantly correlated (r=0.94, p<0.001). The proBNP-108/total BNP (BNP-32+proBNP-108) ratio was widely distributed and lower in HF (0.33 (0.17)) than in control (0.41 (0.06), p<0.05) and AF (0.45 (0.04), p<0.002). The proBNP-108/total BNP ratio was higher in HF with ventricular than in HF with atrial overload (0.45 (0.10) vs 0.20 (0.11), p<0.001). Consistent with this finding, the major molecular form were proBNP-108 and BNP-32 in ventricular (n=6, 0.67 (0.04)) and atrial (n=7, 0.76 (0.05), p<0.0001) tissues, respectively. ProBNP-108 was also the major molecular form of BNP in pericardial fluid (n=8, 0.82 (0.05)). The proBNP-108/total BNP ratio increased and decreased with HF deterioration and improvement, respectively.


CONCLUSIONS
These results suggest that BNP-32 and proBNP-108 is increased in HF and that the proBNP/total BNP ratio increases in association with pathophysiological conditions such as ventricular overload.
Nishikimi
T
T
Department of Hypertension and Cardiorenal Medicine, Dokkyo Medical University, Mibu, Tochigi 321-0293, Japan. nishikim@dokkyomed.ac.jp
Minamino
N
N
Ikeda
M
M
Takeda
Y
Y
Tadokoro
K
K
Shibasaki
I
I
Fukuda
H
H
Horiuchi
Y
Y
Oikawa
S
S
Ieiri
T
T
Matsubara
M
M
Ishimitsu
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000097:blood; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D005260:Female; D006325:Heart Atria / Q000378:metabolism; D006333:Heart Failure / Q000097:blood* / Q000601:surgery; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood* / Q000378:metabolism; D010490:Pericardial Effusion / Q000378:metabolism
D015415:Biomarkers; C524086:Pro-BNP1-108; D020097:Natriuretic Peptide, Brain