Study of nitrolipids in macrophage migration, cholesterol efflux and implication on plaque regression

GUTIERREZ MV; VAZQUEZ MM; CHIABRANDO G; BONACCI G

Parana

Congreso; LIV Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2018

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

In atheroma plaque formation trapping of lipid-laden macrophages in the arteries intima is a critical step and reversion of this process is important for the outcome of atherosclerosis disease. When modified-LDL in the intima is taken up by macrophages, it stimulates uncontrolled lipid accumulation and inhibition of macrophages migration. Nitro-Fatty Acids (NO2-FA) have shown anti-atherogenic effects on ApoE-KO mouse. The aim of this study is to explore the action of nitrolipids on cellular components of the atherosclerotic plaque. In order to this, RAW264.7 macrophages and L6 myoblast migration was evaluated in transwell and wound healing assays in presence of NO2-OA, oleic acid (OA) and curcumin. Results, expressed as cells migrated through the membrane and as percentage of wound closure, showed that NO2-OA increases not only RAW264.7 migration but also abolished the inhibitory effect of oxidized-LDL (oxLDL). L6 migration was not affected by NO2-OA. Plaque regression is characterized by increased macrophages egress from the plaque and cholesterol efflux. Therefore, efflux assays were carried out in RAW267.4 loaded with fluorescent labeled (DiI) oxLDL and efflux was stimulated with NO2-OA in presence of acceptor proteins (serum or HDL). NO2-OA increased the rate lipid efflux as was revealed by fluorescent microscopy but no significant changes were observed in ABCA1 and ABCG1 cholesterol transporters at transcriptional level. In summary, these results represent new contributions for the still unclear mechanisms of regression since NO2-OA may stimulate lipid efflux and modulate macrophages to emigrate from plaque and facilitate their regression.