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

Abstract

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.

• Authors: Lia Millucci, Eugenio Paccagnini, Lorenzo Ghezzi, Giulia Bernardini, Daniela Braconi, Marcella Laschi, Marco Consumi, Adriano Spreafico, Piero Tanganelli, Pietro Lupetti, Agnese Magnani, Annalisa Santucci
• Journal: PloS one (PLoS One) Vol. 6 Issue 7 Pg. e21870 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21814559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid
• Atrial Natriuretic Factor

Topics

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