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Multiple clinical studies have established elevated postprandial triglyceride-rich lipoproteins (TRLs) as an independent risk factor for cardiovascular disease. However, the mechanisms whereby postprandial TRLs, which circulate mostly within chylomicrons, exert their atherogenic effects remain unknown. We have previously reported that media from chylomicron-treated endothelial cells (ECs) leads to lipid droplet (LD) accumulation in cultured macrophages. To determine the reason for this observation, we assessed whether treated ECs produced small extracellular vesicles (sEVs) that were responsible for this effect. When we removed sEVs from the media, LD production diminished. The EVs contained very little free fatty acids and triglycerides, but abundant phospholipids, esp. phosphatidyl serine, and diacylglycerols. Compared to EVs not treated with chylomicrons, these EVs were larger, more abundant, and contained a specific repertoire of microRNAs. Treatment of macrophages with conditioned media increased expression of genes related to several inflammatory processes and genes that promote macrophage adhesion to the vascular wall. In this context, deletion of the endothelial SR-B1, which mediates chylomicrons uptake, mitigates the macrophage inflammatory response at the transcriptional level. Thus, EC chylomicron uptake leads to production of EVs that alter the phenotype of macrophages.
Tilp et al. (Wed,) studied this question.