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|Title:||Different factors affecting human ANP amyloid aggregation and their implications in congestive heart failure.||Authors:||Millucci, Lia
|Keywords:||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||Issue Date:||2011||Project:||None||Journal:||PLOS ONE||Abstract:||
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.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.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.
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