Nitro-fatty acid modulates macrophage lipid metabolism

ACTIS-DATO V; VAZQUEZ M; BONACCI G; CHIABRANDO G

Córdoba

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2016

Sociedad Argentina de Investigación Bioquímica y Biología Molecular

Alteration of lipids metabolism and oxidative balance leads to lipoprotein modification (oxidation or acetylation) and plaque formation. Thus, inflammation and foam cell formation are important components in the initiation and progression of atherosclerosis. We have demonstrated that activated macrophages form bioactive lipids mediators named nitro-fatty acid (NO2-FA), which exhibit important anti-inflammatory and cytoprotective actions in experimental model of cardiovascular disease. In this work we evaluated the action of NO2-FA to modulate lipid uptake and foam cell formation on RAW264.7 macrophage cell line. NO2-OA increased membrane expression of scavenger receptors LRP-1 and CD36 in a dose dependent manner. This up-regulation is transient and reaches a maximum at 8h, which was not affected by treatment with cycloheximide. These results allow us to speculate that modulation of LRP-1 and CD36 expression by nitrolipids affect protein stability. Uptake of oxidized LDL particles in RAW264.7 macrophages treated with NO2-OA result in an increased lipid accumulation as reveled by Oil Red O staining of lipids droplets. However, we observed that NO2-OA improved the autophagic flux by inducing LC3II accumulation. This result may explain, in part, the beneficial action ascribed to NO2-FAs in atherosclerosis by balancing the intracellular lipid content and foam cell formation.