Role of Nitro-Fatty Acids in the regulation of scavenger receptors and foam cell formation

VAZQUEZ M; REYES, AB; ACTIS-DATO V; CHIABRANDO G; BONACCI G

Mar del Plata, Buenos Aires

Congreso; LI Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2015

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Nitro-fatty acids (NO2-FA) are potent lipids signaling mediators formed from nitric oxide and nitrite dependent reaction. NO2-FA modulates signaling cascades via covalent posttranslational modification (PTM) to important regulatory proteins, thus affecting downstream signaling events, such as the NF-κB, PPARγ and Keap1-Nrf2 pathways. We have previously demonstrated that macrophages form nitro-conjugated linoleic acid (NO2-CLA) under inflammatory condition and they exhibit important anti-inflammatory and cytoprotective actions in vitro and in vivo. In the present work we explored the ability of NO2-FA to modulate the expression of scavenger receptors (CD36, SRA and LRP-1) on RAW264.7 and THP-1 macrophage cell line. Nitro-oleic acid (NO2-OA) induced CD36 expression and exhibited slight effect on LRP-1 and SRA expression. This up-regulation of CD36 receptor was linked to the electrophilic activation of the antioxidant transcription factor Nrf2 by NO2-FA. Thus, uptake of modified LDL particles in macrophage treated with NO2-OA result in an increase lipid accumulation by appearance of Red Oil O positive lipids droplets compared to untreated cells. Our results indicate that NO2-FA induce foam cell formation in vitro and challenged the understanding between anti-inflammatory and anti-atherogenic action of NO2-FA during plaque formation in atherosclerosis.