Transport of Apolipoprotein B-Containing Lipoproteins through Endothelial Cells Is Associated with Apolipoprotein E-Carrying HDL-Like Particle Formation

Abstract

Passage of apolipoprotein B-containing lipoproteins (apoB-LPs), i.e., triglyceride-rich lipoproteins (TRLs), intermediate-density lipoproteins (IDLs), and low-density lipoproteins (LDLs), through the endothelial monolayer occurs in normal and atherosclerotic arteries. Among these lipoproteins, TRLs and IDLs are apoE-rich apoB-LPs (E/B-LPs). Recycling of TRL-associated apoE has been shown to form apoE-carrying high-density lipoprotein (HDL)-like (HDLE) particles in many types of cells. The current report studied the formation of HDLE particles by transcytosis of apoB-LPs through mouse aortic endothelial cells (MAECs). Our data indicated that passage of radiolabeled apoB-LPs, rich or poor in apoE, through the MAEC monolayer is inhibited by filipin and unlabeled competitor lipoproteins, suggesting that MAECs transport apoB-LPs via a caveolae-mediated pathway. The cholesterol and apoE in the cell-untreated E/B-LPs, TRLs, IDLs, and LDLs distributed primarily in the low-density (LD) fractions (d ≤ 1.063). A substantial portion of the cholesterol and apoE that passed through the MAEC monolayer was allotted into the high-density (HD) (d > 1.063) fractions. In contrast, apoB was detectable only in the LD fractions before or after apoB-LPs were incubated with the MAEC monolayer, suggesting that apoB-LPs pass through the MAEC monolayer in the forms of apoB-containing LD particles and apoE-containing HD particles.

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases

“…Although one could argue that cord cells do not reflect the physiology of brain vasculature, we and others have previously demonstrated that HUVECs express BBB marker proteins when cocultured with astrocytes 11,54,55 . Further, we have demonstrated here that apoE is restricted in the abluminal chamber in our model; a feature characteristic of BBB EC, given that apoE is actively transported through peripheral ECs 56,57 . Another limitation is that we used primary cells for the vascular cells over iPSC-derived cells.…”

Sphingolipid metabolism in the pathophysiology and treatment of Alzheimer’s disease

“…These few examples clearly demonstrate that the simplified view on the rheostat of ceramide and S1P as pro-and anti-apoptotic balance will need to be replaced by a more mechanistically refined model invoking specific interaction with rafts and proteins regulating cell signaling pathways in neural development and disease. HDL, which is predominantly produced in the liver and intestine, lacks ApoB and is instead mainly accompanied by ApoA-I [150]. ApoE4, one of the 3 common isoforms of ApoE (E2, E3, and E4),…”

“…ApoE is carried by chylomicrons, VLDL, and a subclass of HDL. HDL containing ApoE is formed when triglyceride-rich lipoproteins, such as VLDL and chylomicrons release fatty acids upon lipolysis [150]. Circulating ApoE4 prefers association with VLDL and chylomicrons, while ApoE3 prefers HDL [152].…”

Lipids and lipid transporters

“…The carrier apolipoprotein (Apo) of liver-derived lipoproteins, VLDL and LDL, is apoB100, while that of the lipoproteins of the intestine, chylomicrons, is apoB48. HDL, which is predominantly produced in the liver and intestine, lacks ApoB and is instead mainly accompanied by ApoA-I [155]. ApoE4, one of the 3 common isoforms of ApoE (E2, E3, and E4), is linked with a strongly increased risk of developing AD [156].…”

“…ApoE is carried by chylomicrons, VLDL, and a subclass of HDL. HDL containing ApoE is formed when triglyceride-rich lipoproteins, such as VLDL and chylomicrons release fatty acids upon lipolysis [155]. Circulating ApoE4 prefers association with VLDL and chylomicrons, while ApoE3 prefers HDL [157].…”