TNF?-Induced LDL Cholesterol Accumulation Involve Elevated LDLR Cell Surface Levels and SR-B1 Downregulation in Human Arterial Endothelial Cells

Excess lipid droplets are frequently observed in arterial endothelial cells at sites of advanced atherosclerotic plaques. Here, the role tumor necrosis factor alpha (TNF?) modulating low-density lipoprotein (LDL) content confluent primary human aortic (pHAECs) was investigated. TNF? promoted an up to 2 folds increase cellular cholesterol, which resistant ACAT inhibition. The cholesterol associated with increased 125I-LDL surface binding. Using non-hydrolysable label, Dil, could induce a massive Dil-LDL by over 200 folds. elevated intracellular blocked excess unlabeled LDL and PCSK9, but not oxidized (oxLDL), or apolipoprotein (apoE) depletion. Moreover, TNF?-induced LDL-derived lipids through lysosome specific LDLR antibody, accumulation reduced 99%. effects included cell 138%, very large increases ICAM-1 total proteins, respectively. In contrast, that scavenger receptor B1 (SR-B1) reduced. Additionally, antibody bound rapidly TNF?-treated about 30 folds, inducing migrating shift protein. effect on inhibited antioxidant tetramethythiourea (TMTU) dose-dependently, inhibitors against NF-?B, stress kinases, ASK1, JNK, p38, apoptosis caspases. Grown Transwell inserts, did enhance apical basolateral Dil release. It is concluded promotes functions combined SR-B1 downregulation.