Nitro fatty acids modulate lipid content and inflammatory profile of peripheral blood monocytes at early stages of atherosclerosis in ApoE-/- mice.

GUTIERREZ, MARIA V.; CHIABRANDO G; SCHOPFER FJ; BONACCI G

Louisiana

Congreso; Regional Redox Symposium. Redox Pathophysiology in Health and Disease; 2024

SFRBM

Atherosclerosis is a chronic inflammatory disease associated with an imbalance of lipid metabolism and activation of innate immune cells (IICs). Hypertriglyceridemia induces lipid accumulation in peripheral blood monocytes (PBM), increasing the number of lipid droplets and driving to foamy monocyte formation. These cells have an inflammatory phenotype and express markers of monocyte activation and differentiation to macrophages. Changes in PBM occur at the early stage of cardiovascular disease and are associated with migration across vascular endothelium. Nitro-fatty acid (NO2-FA) inhibits atheroma plaque development in Apo E-/- mice, characterized by an increase in plaque stability and a decrease in cellular infiltration. Thus, the present work aims to study whether NO2-FA can modulate lipid metabolism and inflammatory profile in monocytes and their impact in the early stage of atherosclerosis. To carry out this objective, we have designed two experimental models: a) ApoE-/- mice fed with a Western diet (WD) or Normal diet (ND) and b) cellular culture of THP-1 human monocytes. Blood samples obtained by submandibular vein draw at 0, 15, and 30 days of diet were labeled to study the expression of scavenger receptors (SRs) in monocytes by flow cytometry. At the end of the diet, aortas were obtained to perform immunofluorescence and ORO staining. Moreover, mononuclear cells were isolated for cell culture. Our results showed that ApoE-/- mice develop atherosclerotic plaque after two months of WD and that the atheroma plaque presents a high expression of LRP1. The longitudinal PBM analysis indicates that SRs, LRP1, and CD36, increased at day 15 in ApoE-/- compared to C57BL/6 mice (p