Boosting cholesterol efflux from foam cells by sequential administration of RHDL to deliver microRNA and to remove cholesterol in a triple-cell two-dimensional atherosclerosis model

Background and Aims : Cardiovascular disease, the leading cause of mortality worldwide, is primarily caused by atherosclerosis, which characterized lipid inflammatory cell accumulation in blood vessels carotid intima thickening, among others. Although disease management has improved significantly, new therapeutic strategies focused on accelerating atherosclerosis regression must be developed. Atherosclerosis models mimicking vivo-like conditions provide essential information for research advances towards clinical application.Methods: Here a strategy to improve cholesterol efflux been developed based two-step administration rHDL consisting first dose antagomiR-33a-loaded rHDLs induce ABCA1 transporter overexpression, followed second DPPC rHDLs, remove efficiently from foam cells. A triple-cell 2D atheroma plaque model reflecting cellular complexity used overcome translational gap providing suitable efficiency nanoparticles promoting efflux.Results: The results show that sequential potentiates indicating this approach might vivo target more atherosclerotic lesions prognosis disease.Conclusions: Sequential targeting cells with including antagomiR-33a delivery DPPC:CE:LPC infusion induces potent cells, may current technique barriers promote applications. application. Methods: efflux. Results: disease. Conclusions: