Extracellular Vesicles From Chylomicron-Treated Endothelial Cells Drive Macrophage Inflammation

作者：Anna Tilp, Dimitris Nasias, Andrew L. Carley, Min Young Park, Ashley Mooring, Munichandra Babu Tirumalasetty, Nada A. Abumrad, Yang Wang, Qing Miao, E. Douglas Lewandowski, José O. Alemán, Ira J. Goldberg, Ainara G. Cabodevilla · 发表于：Arteriosclerosis Thrombosis and Vascular Biology · 年份：2025 · DOI：10.1161/atvbaha.125.322712 · 被引用次数：4 · 研究领域：Extracellular vesicles in disease、Immune cells in cancer、Caveolin-1 and cellular processes

BACKGROUND: Movement of circulating lipids into tissues and arteries requires transfer across the endothelial cell (EC) barrier. This process allows the heart to obtain fatty acids, its chief source of energy, and apoB-containing lipoproteins to cross the arterial endothelial barrier, leading to cholesterol accumulation in the subendothelial space. Multiple studies have established elevated postprandial TRLs (triglyceride-rich lipoproteins) as an independent risk factor for cardiovascular disease. We explored how chylomicrons affect ECs and transfer their fatty acids across the EC barrier. METHODS: We had reported that media from chylomicron-treated ECs lead to lipid droplet formation in macrophages. To determine the responsible component of this media, we assessed whether removing the extracellular vesicles (EVs) would obviate this effect. EVs from control and treated cells were then characterized by protein, lipid, and microRNA content. We also studied the EV-induced transcription changes in macrophages and ECs and whether knockdown of SR-BI (scavenger receptor-BI) altered these responses. In addition, using chylomicrons labeled with [ 13 C]oleate, we studied the uptake and release of this labeled by ECs. RESULTS: Chylomicron treatment of ECs led to an inflammatory response that included production of EVs that drove macrophage lipid droplet accumulation. The EVs contained little free fatty acids and triglycerides, but abundant phospholipids and diacylglycerols. In concert w...