STIMULATION OF INFLAMMATORY MICROENVIRONMENT BY A HUMAN APOLIPOPROTEIN A-I NATURAL VARIANT

GISONNO, ROMINA; EIGUREN, AC; ROSU, S. A; CALABRESE, GRACIELA C.; TRICERRI, M. A.; RAMELLA, N. A

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

SAIC. SAFE. SAB. SAP

The cascade of molecular events leading to human apolipoprotein A?I (apoA?I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. Among more than twenty natural variants of apoA-I, it was shown that the substitution of an Arg in position 173 by a Pro in the sequence of apoA-I (R173P) induced heart amyloidosis. The mechanisms determining its pathogenicity are not clear. In this work, we gained deep insight into cellular events probably elicited by the soluble conformation of R173P. WT apoA-I and R173P were obtained by molecular biology techniques. Human umbilical vein endothelial cells (HUVEC) or a human monocyte-derived cellular line (THP-1) were treated with 1.5 µg/ml for 24 h. Immunofluorescence of NFkB was used to evaluate endothelial activation; and enzyme immunoassays (ELISA) were performed to evaluate tumor necrosis factor (TNF) alpha; and interleukin (IL)-1ß. We detected that the natural variant R173 induced NFkB translocation into the nucleus of endothelial cells. Moreover, the incubation of R173P with THP-1 resulted in the release of tumor necrosis TNF- alpha (p