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- W4313014033 abstract "The development of atherosclerosis is triggered by the endothelial crossing and subendothelial retention of apolipoprotein B (ApoB)-containing LDL and chylomicron remnants. LDL has been reported to cross the endothelial cell (EC) barrier via two receptors: scavenger receptor-B1 (SR-B1) and activin receptor-like kinase 1 (ALK1). We have shown that SR-B1 also mediates EC uptake of nascent chylomicrons, leading to the accumulation of lipid droplets (LD) within the aortic endothelium and skin macrophages of hyperchylomicronemic LpL-deficient mice. In vitro, chylomicron-exposed ECs induced LD accumulation in co-cultured macrophages in the absence of any other lipid source. Surprisingly, conditioned media from chylomicron-exposed ECs primarily contained phospholipids and diglycerides, rather than triglycerides and fatty acids. Electron microscopy analysis revealed the presence of small extracellular vesicles (sEVs), and filtration of the media to remove sEVs prevented LD accumulation in macrophages. To determine the molecular interaction of chylomicrons and SR-B1 we performed a series of competition experiments. At physiologic concentrations found in postprandial blood, chylomicrons blocked LDL uptake into cultured ECs. Moreover, chylomicron uptake was blocked by co-incubation with ApoB18, a lipid-free peptide comprising the 18% N-terminus of ApoB. To assess this in vivo, we used an adeno-associated virus to overexpress ApoB18 in LpL-deficient mice. ApoB18-expressing mice exhibited a ≈ 50% reduction in aortic EC LD content, suggesting that the peptide effectively inhibits chylomicron uptake in vivo. Further, ApoB18 blocked LDL uptake by ECs in culture. These results suggest that a) the N-terminus of ApoB harbors a binding sequence for SR-B1 and b) endothelial uptake of both chylomicrons and LDL can be blocked by competition with non-lipoprotein ApoB peptides." @default.
- W4313014033 created "2023-01-05" @default.
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- W4313014033 date "2022-05-01" @default.
- W4313014033 modified "2023-09-26" @default.
- W4313014033 title "Abstract 115: N-terminus Of ApoB Mediates Endothelial Cell Chylomicron Uptake" @default.
- W4313014033 doi "https://doi.org/10.1161/atvb.42.suppl_1.115" @default.
- W4313014033 hasPublicationYear "2022" @default.
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