REGULATION OF LRP1 EXPRESSION BY MODIFIED LDL AND NITRO-FATTY ACIDS IN MACROPHAGES

GUTIERREZ MV; VAZQUEZ MM; ACTIS DATO V; CHIABRANDO G.; BONACCI G

Congreso; LVII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2021

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

Atherosclerosis is a chronic inflammatory disease strongly associated with dyslipidemia and activation of innate immune cells (IICs), such as peripheral blood monocytes (PBM) and macrophages. The low density lipoprotein receptor-related protein 1 (LRP1) is a member of the LDL-receptor family, which is expressed in monocytes and macrophages. LRP1 has an active participation in the promotion of pro-inflammatory profiles in these cells during atherosclerosis. Previously we demonstrated a reduced expression of LRP1 in PBM of individuals with subclinical atherosclerosis. Moreover, the expression of LRP1 can be affected by the presence of modified LDL (modLDL), mainly as aggregated LDL and oxidized LDL, which may be an extracellular factor to promote pro-inflammatory profiles in IICs. Our work group also described that nitro-fatty acids (NO2-OA), an endogenous bioactive lipid derivative, modulate expression and intracellular signaling activation of CD36, a scavenger receptor involved with the inflammatory status of macrophages. However, the effect of NO2-OA on the LRP1 expression is unknown. Thus, the aim of the present work is to study the relationship between LRP1 expression and inflammatory profiles in macrophages treated with modLDL and establish whether this effect may be countered by NO2-OA. As experimental models we used THP-1 and RAW264.7 macrophage-derived cells, which were cultured with modLDL (100 μg/ml) for different times and then, incubated in the presence or absence of NO2-OA (5 μM). Next, the expressions of LRP1 and pro-inflammatory factors as well as reactive-oxygen species (ROS) were analyzed. In this cellular model, treatment with modLDL impaired macrophage migration, promoted ROS generation and induced pro-inflammatory factors, such as IL6. This pro-inflammatory profile obtained in macrophages, after treatment with modLDL, was countered by NO2-OA, promoting an increase in LRP1 expression, inhibition in ROS generation and pro-inflammatory expression. All together these results indicate that LRP1 has an active participation in the production of pro-inflammatory profiles in macrophages, which may be regulated by modLDL produced in dyslipidemia disorder.