HUMAN APOLIPOPROTEIN A-I IN ATHEROSCLEROSIS. THE ROLE OF OXIDATION OR NATURAL VARIANTS SYNERGIZING ITS DYSFUNCTION.

IVO DÍAZ LUDOVICO; GONZALEZ, MARINA C.; RODRIGUEZ E.; ROMINA A. GISONNO; CORTEZ F.; GORGOJO J. P.; NAHUEL RAMELLA; ROSÚ, S.A.; GARDA, H.; MARÍA ALEJANDRA TRICERRI

Buenos Aires

Congreso; ANNUAL MEETING OF BIOSCIENCE SOCIETIES 2020; 2020

SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC)

Oxidation of human high density lipoprotein and its major proteinapolipoprotein A-I (apoA-I) was proposed to cause their failure toprotect against cardiovascular disease. However, multiple and complex events might contribute to the breakdown of this protein to fulfillits protective role. To set light on this topic, we took advantage of thestudy of a natural variant with a deletion of the lysine 107 (K107del)associated with atherosclerosis and amyloidosis. We oxidized thevariants by controlled incubation with H2O2 and determined structural and biological parameters by biophysical and biological approaches.Both variants oxidized under these conditions preserved or eveninduced an increase in the lipid clearance with respect to untreated proteins (20 % with p ≤ 0.05), and decreased the yield of thephysiological dimeric conformations. Following 30-day incubation at37oC K107del but not Wt acquired a well-defined fibrillar conformation which is the main signature of the amyloid pathology. Theseconformations (but not freshly folded proteins) activated neutrophilsinto the formation of neutrophil extracellular traps (NETs) (p