HUMAN APOLIPOPROTEIN A-I IN ATHEROSCLE ROSIS. THE ROLE OF OXIDATION OR NATURAL VARI ANTS SYNERGIZING ITS DYSFUNCTION.

DÍAZ LUDOVICO, I.; GONZALEZ, M; RODRIGUEZ, M. EUGENIA; ROSU, S. A; GARDA, H; TRICERRI, M. A.; GISONNO, ROMINA; CORTEZ, M. FERNANDA; GORGOJO, JUAN P.; RAMELLA, NAHUEL A.

Buenos Aires

Encuentro; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2020; 2020

SAIC. SAI SAFIS

Oxidation of human high density lipoprotein and its major protein apolipoprotein A-I (apoA-I) was proposed to cause their failure to protect against cardiovascular disease. However, multiple and complex events might contribute to the breakdown of this protein to fulfil its protective role. To set light on this topic, we took advantage of the study of a natural variant with a deletion of the lysine 107 (K107del) associated with atherosclerosis and amyloidosis. We oxidized the variants by controlled incubation with H2O2 and determined structural and biological parameters by biophysical and biological approaches. Both variants oxidized under these conditions preserved or even induced an increase in the lipid clearance with respect to untreated proteins (20 % with p = 0.05), and decreased the yield of the physiological dimeric conformations. Following 30-day incubation at 37Oc K107del but not Wt acquired a well-defined fibrillar conformation which is the main signature of the amyloid pathology. These conformations (but not freshly folded proteins) activated neutrophils into the formation of neutrophil extracellular traps (NETs) (p