An N-terminal pro-atrial natriuretic peptide (NT-proANP) 'aggregation-prone' segment involved in isolated atrial amyloidosis

FEBS Lett. 2014 Jan 3;588(1):52-7. doi: 10.1016/j.febslet.2013.10.049. Epub 2013 Nov 9.

Abstract

Isolated atrial amyloidosis (IAA) is a common localized form of amyloid deposition within the atria of the aging heart. The main constituents of amyloid fibrils are atrial natriuretic peptide (ANP) and the N-terminal part of its precursor form (NT-proANP). An 'aggregation-prone' heptapeptide ((114)KLRALLT(120)) was located within the NT-proANP sequence. This peptide self-assembles into amyloid-like fibrils in vitro, as electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and Congo red staining studies reveal. Consequently, remedies/drugs designed to inhibit the aggregation tendency of this 'aggregation-prone' segment of NT-proANP may assist in prevention/treatment of IAA, congestive heart failure (CHF) or atrial fibrillation (AF).

Keywords: AF; ANP; ATR FT-IR spectroscopy; Amyloid fibril; BNP; CHF; Cardiac amyloidose; IAA; Isolated atrial amyloidosis (IAA); N-terminal pro-atrial natriuretic peptide; N-terminal pro-atrial natriuretic peptide (NT-proANP); NT-proANP; Natriuretic peptide; SSA; TTR; atrial fibrosis; atrial natriuretic peptide; attenuated total reflectance Fourier-transform spectroscopy; brain natriuretic peptide; cGMP; congestive heart failure; cyclic guanosine monophosphate; isolated atrial amyloidosis; senile systemic amyloidosis; transthyretin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry
  • Amyloid / metabolism
  • Amyloid / ultrastructure
  • Amyloidosis / metabolism*
  • Atrial Natriuretic Factor / chemistry
  • Atrial Natriuretic Factor / genetics
  • Atrial Natriuretic Factor / metabolism*
  • Congo Red / chemistry
  • Heart Atria / metabolism
  • Heart Atria / pathology
  • Humans
  • Microscopy, Electron
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism*
  • Protein Precursors / chemistry
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Spectroscopy, Fourier Transform Infrared
  • X-Ray Diffraction / methods

Substances

  • Amyloid
  • Peptide Fragments
  • Protein Precursors
  • Congo Red
  • Atrial Natriuretic Factor