title: Different factors affecting human ANP amyloid aggregation and their implications in congestive heart failure.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Dipartimento di Biotecnologie, Università degli Studi di Siena, Siena, Italy.
authors.forename: Lia
authors.initials: L
authors.lastname: Millucci
authors.forename: Eugenio
authors.initials: E
authors.lastname: Paccagnini
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghezzi
authors.forename: Giulia
authors.initials: G
authors.lastname: Bernardini
authors.forename: Daniela
authors.initials: D
authors.lastname: Braconi
authors.forename: Marcella
authors.initials: M
authors.lastname: Laschi
authors.forename: Marco
authors.initials: M
authors.lastname: Consumi
authors.forename: Adriano
authors.initials: A
authors.lastname: Spreafico
authors.forename: Piero
authors.initials: P
authors.lastname: Tanganelli
authors.forename: Pietro
authors.initials: P
authors.lastname: Lupetti
authors.forename: Agnese
authors.initials: A
authors.lastname: Magnani
authors.forename: Annalisa
authors.initials: A
authors.lastname: Santucci
mesh_terms: D000682:Amyloid / Q000378:metabolism* / Q000648:ultrastructure; D000686:Amyloidosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology*; D006333:Heart Failure / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D006339:Heart Rate; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; D009320:Atrial Natriuretic Factor