LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN-1 EXPRESSION ON MONOCYTES/MACROPHAGES OF APOE -/- MICE

GUTIERREZ MV; CASALE R; CHIABRANDO G; BONACCI G

Mar del Plata

Congreso; LXVII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

Atherosclerosis is a chronic inflammatory disease associated withimbalance of lipid metabolism and activation of innate immunecells (IICs) expressing low density lipoprotein receptor-relatedprotein 1 (LRP1) such as peripheral blood monocytes (PBM) andmacrophages. LRP1 has an active participation in the modulationof inflammatory profile in monocytes/macrophages during atherosclerosis.Recently, our group has demonstrated a decrease in theexpression of LRP1 in PBM of individuals with subclinical atherosclerosis.Thus, the aim of the present work is to study the expressionlevel of scavenger receptors, LRP1 and CD36, and intracellularlipid content in PBM at early stage of atherosclerosis disease. Tocarry out this objective, ApoE-/- and wild type (C57BL/6) mice werefed with a high fat diet (HFD) or normal diet (ND) for 3 months. Forflow cytometry, blood samples were obtained by submandibular veindraw at 0, 15, 30 and 75 days of diet from the same animal andlabeled with following antibodies LRP1-APC, CD36-APC, CD115-APC Cy7, Bodipy-FITC, Ly6G-PE, CD3-PE and CD19-PE. In addition,aortas and blood (cardiac puncture) for Ficoll isolation of totalmononuclear cells were collected at 0, 30, 75 and 90 days for immunofluorescence,Oil Red O for lipid staining and cells for qPCRassays. Our results shown that ApoE-/- mice develop atheroscleroticplaque after 2 months of HFD diet and the expression of LRP1 increasesignificantly into the atheroma plaque. From the longitudinalanalysis of PBM, we observed that LRP1 expression is significantlyincreased at day 15 compared to wild type mice (p<0,05) and CD36had a similar trend. This group of monocytes showed high intracellularlipid content with correlate with increased expression of CD36.These results suggest that LRP1 expression in PBM changes inearly stages of atherosclerotic plaque formation and may be relatedwith the pro-inflammatory stage of circulating monocytes.