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

RAMELLA NA, RIMOLDI OJ, PRIETO ED, SCHINELLA GR, SANCHEZ SA, JAUREGUIBERRY MS, VELA ME, FERREIRA ST, TRICERRI MA.

PLOS ONE

PUBLIC LIBRARY SCIENCE

Año: 2011 vol. 6 p. 22532 - 22532

1932-6203

Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-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.