Different factors affecting human ANP amyloid aggregation and their implications in congestive heart failure

PLoS One. 2011;6(7):e21870. doi: 10.1371/journal.pone.0021870. Epub 2011 Jul 26.


Aims: Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis.

Methods and results: A significant prevalence (85%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA.

Conclusions: We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / metabolism*
  • Amyloid / ultrastructure
  • Amyloidosis / complications*
  • Amyloidosis / metabolism
  • Amyloidosis / pathology*
  • Atrial Natriuretic Factor / metabolism*
  • Blood Pressure
  • Electrophoresis, Polyacrylamide Gel
  • Female
  • Heart Atria / metabolism
  • Heart Atria / pathology*
  • Heart Failure / etiology*
  • Heart Failure / metabolism
  • Heart Failure / pathology*
  • Heart Rate
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Risk Factors
  • Spectroscopy, Fourier Transform Infrared


  • Amyloid
  • Atrial Natriuretic Factor