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An amyloidogenic determinant in n‐terminal pro‐brain natriuretic peptide (nt‐probnp): Implications for cardiac amyloidoses
Author(s) -
Iconomidou Vassiliki A.,
Pheida Danae,
Hamodraka Eftihia S.,
Antony Claude,
Hoenger Andreas,
Hamodrakas Stavros J.
Publication year - 2011
Publication title -
peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21698
Subject(s) - chemistry , natriuretic peptide , medicine , amyloid (mycology) , brain natriuretic peptide , amyloidosis , atrial natriuretic peptide , prohormone , npr2 , peptide , endocrinology , heart failure , biochemistry , hormone , inorganic chemistry
Abstract Deposition of amyloid in the atria (isolated atrial/cardiac amyloid) is fairly common in the aging heart. It consists of amyloid fibrils, formed both by atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and the precursor molecule of ANP, proANP. This study examines whether amyloidogenic determinants (short peptides/amyloid forming favoring regions) exist in the sequence of NT‐proBNP, the N‐terminal part of proBNP, and if these determinants form amyloid‐like fibrils in vitro. We have predicted a possible amyloidogenic determinant in the sequence of the NT‐proBNP, and we conclusively show, after its synthesis, that it forms amyloid‐like fibrils in vitro, utilizing transmission electron microscopy, X‐ray diffraction, attenuated total reflectance Fourier‐transform infrared spectroscopy, and polarizing microscopy. Thus, for the first time, in this study, a possible biological role is attributed to a certain, specific part of this important cardiac prohormone/natriuretic peptide, which acts as an important biomarker indicative of heart failure. Its possible direct involvement in isolated cardiac amyloidosis, atrial fibrillation, and other types of cardiac amyloidoses is indicated and discussed. Since these cardiac hormones and their prohormones play key roles in cardiovascular homeostasis through natriuresis, diuresis, vasorelaxation, and inhibition of renin and aldosterone secretion (pathophysiology of hypertension and cardiovascular regulation), we also try to suggest these specific, short peptides as possible future structural targets of efforts toward inhibiting formation of natriuretic peptide(s) amyloid. © 2011 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 98: 67–75, 2012.