title: Human apolipoprotein A-I-derived amyloid: its association with atherosclerosis.
abstract: Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis.
authors.affiliation: Instituto de Investigaciones Bioquímicas La Plata (INIBIOLP), CCT-CONICET, La Plata, Argentina.
authors.forename: Nahuel A
authors.initials: NA
authors.lastname: Ramella
authors.forename: Omar J
authors.initials: OJ
authors.lastname: Rimoldi
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Prieto
authors.forename: Guillermo R
authors.initials: GR
authors.lastname: Schinella
authors.forename: Susana A
authors.initials: SA
authors.lastname: Sanchez
authors.forename: María S
authors.initials: MS
authors.lastname: Jaureguiberry
authors.forename: María E
authors.initials: ME
authors.lastname: Vela
authors.forename: Sergio T
authors.initials: ST
authors.lastname: Ferreira
authors.forename: M Alejandra
authors.initials: MA
authors.lastname: Tricerri
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D000817:Anilino Naphthalenesulfonates / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D050197:Atherosclerosis / Q000378:metabolism*; D052160:Benzothiazoles; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006493:Heparin / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006997:Hypochlorous Acid / Q000494:pharmacology; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D018375:Neutrophil Activation / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D059748:Proteolysis / Q000187:drug effects; D012997:Solvents; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013844:Thiazoles / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism
chemical_list: C505693:APOA1 protein, human; D000682:Amyloid; D000817:Anilino Naphthalenesulfonates; D016632:Apolipoprotein A-I; D052160:Benzothiazoles; D012997:Solvents; D013844:Thiazoles; C009462:thioflavin T; C035763:5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate); D006997:Hypochlorous Acid; D014364:Tryptophan; D006493:Heparin; D002784:Cholesterol; D053508:Matrix Metalloproteinase 12; D013755:Tetradecanoylphorbol Acetate