Human apolipoprotein A-I-derived amyloid: its association with atherosclerosis

• Autores: Ramella, Nahuel; Rimoldi, Omar J.; Prieto, Eduardo Daniel; Sánchez, Susana; Jaureguiberry, M. Soledad; Ferreira, Sergio T.; Tricerri, Alejandra; Schinella, Guillermo Raúl; Vela, María Elena
• Año de publicación: 2011
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: Ciencias Médicas y de la Salud; Bioquímica y Biología Molecular; Amiloidosis; Apolipoproteína A-I
• Institución: Comisión de Investigaciones Científicas de la Provincia de Buenos Aires

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.