Human Apolipoprotein A-I-Derived Amyloid: Its Association with Atherosclerosis

RAMELLA, NAHUEL; RIMOLDI, OMAR; BIOQ. PRIETO E.D; SCHINELLA, GUILLERMO; SANCHEZ, SUSANA; JAUREGUIBERRY,MARÍA S.; MARÍA E. VELA; SERGIO T. FERREIRA; TRICERRI, M. ALEJANDRA

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2011 p. 1 - 11

1932-6203

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 atheroscleroticarteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this workwe investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated withchronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pHpromotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring proteindeposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the proteingive rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it mayproduce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated toatherogenesis.