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- The role of peripheral blood mononuclear cells in atherogenesisPublication . Simões Martins Bispo, Cláudia; Crespo, Ana Maria Viegas; Costa, Luciana Maria Gonçalves daAtherosclerosis (ATH) is recognized as a chronic inflammatory condition and it is the leading cause of cardiovascular disease. Atherogenesis is characterized by the infiltration of low density lipoprotein (LDL) through the endothelial layer, and migration of activated peripheral blood lymphocytes (PBL) and monocytes (PBMN) that contribute to a pro-inflammatory state in specific locations. However, the functional interaction between immunity and LDL metabolism is still not fully understood. One hypothesis for the etiopathogeny of ATH may be associated with an ongoing inflammatory process caused by a pro-oxidant/anti-oxidant imbalance induced by metals such as iron (Fe) or copper (Cu). Interestingly, ceruloplasmin (Cp) is a multicopper oxidase with a relevant role in Fe metabolism and oxidation of LDL, but also an acute-phase protein involved in the inflammatory process. Herein, we intended to study by flow cytometry the effect of putative pro-atherogenic immune stimuli on the expression of Cp at the surface of human peripheral blood mononuclear cells (PBMC), and search for a putative association with LDL oxidation. Additionally, a population of Familial Hypercholesterolemia (FH) patients was used as a clinical model of ATH to clarify the physiologic interplay between inflammation, Fe/Cu and lipid metabolism at systemic level in this disease. The obtained results showed that higher cell surface expression of Cp was consistently observed in PBMN compared to PBL, in activated vs non-activated cells and in non-T cells vs T cells. Also, PBMC surface expression of Cp was differently modulated by several tested treatments. In particular, various modulators caused opposite effects on Cp expression of PBMN compared to PBL, suggesting a specific cell-type regulation for this protein. Specifically, it was observed that different sources of Fe might activate specific regulation mechanisms of Cp. Until now, due to technical limitations it was not possible to demonstrate an association between PBMC surface Cp expression and oxidation of LDL, but this issue should be addressed in future experiments. Of notice, IL-1β which was found to significantly increase PBMN surface Cp expression in vitro, was increased in serum from FH patients and positively correlated with total cholesterol and ApoB. However, the fact that no correlation was found between IL-1β and serum Cp (sCp)/oxidated LDL suggest that at systemic level, IL-1β may not be a contributing factor for oxidation of LDL by sCp. However, the role of PBMC surface Cp expression on LDL oxidation, namely in specific inflammatory states, remains to be established. In summary, the results of this study demonstrate that specific pro-atherogenic conditions are involved in the modulation of Cp expression at surface of PBMC and thus, suggest a possible a role of Cp in ATH.