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
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.