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

RAMELLA, N.; RIMOLDI. O. J.; PRIETO, E. D.; SCHINELLA, GUILLERMO; SANCHEZ, S. A.; JAUREGUIBERRY, M. S.; VELA, M E. ; FERREIRA, S. T.; TRICERRI, M. A. (*AUTOR CORRESPOND)

PLOS ONE

PUBLIC LIBRARY SCIENCE

Año: 2011 vol. 6 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 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.