PLoS By Category | Recent PLoS Articles

Biochemistry - Biophysics - Geriatrics


Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure
Published: Tuesday, July 26, 2011
Author: Lia Millucci et al.

by Lia Millucci, Eugenio Paccagnini, Lorenzo Ghezzi, Giulia Bernardini, Daniela Braconi, Marcella Laschi, Marco Consumi, Adriano Spreafico, Piero Tanganelli, Pietro Lupetti, Agnese Magnani, Annalisa Santucci

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 a-ANP as well as the ability of dimeric ß-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing ß-ANP prevalence in CHF. Our results defined the uncommon rapidity of a-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 ß-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that ß-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.

  More...

 
//-->