High-density lipoprotein endocytosis in endothelial cells

Area of Science:

• Cell Biology
• Lipid Metabolism
• Vascular Biology

Background:

• High-density lipoprotein (HDL) plays a crucial role in reverse cholesterol transport.
• Understanding HDL uptake mechanisms in endothelial cells is vital for cardiovascular health.
• Previous studies have suggested various pathways for HDL interaction with cells.

Purpose of the Study:

• To elucidate the detailed mechanisms of HDL uptake and lipid exchange within endothelial cells.
• To investigate HDL trafficking in both in vitro and in vivo models.
• To compare HDL processing in endothelial cells with that in hepatic cells.

Main Methods:

• Utilized fluorescence and electron microscopy with novel fluorescent cholesterol surrogates.
• Employed radio-labeled HDL particles to quantify cellular uptake.
• Validated in vitro findings in mice by analyzing fluorescently labeled HDL uptake in the liver.

Main Results:

• HDL uptake in human endothelial cells occurs via clathrin-coated pits, tubular endosomes, and multivesicular bodies.
• HDL-derived cholesterol exchange was rapid, similar to pathways in hepatic cells, without lysosomal degradation.
• In vivo studies showed HDL primarily in mouse hepatic endothelial cells, not parenchymal cells, suggesting selective lipid uptake.

Conclusions:

• Endothelial cells internalize HDL through clathrin-coated pits, tubular endosomes, and multivesicular bodies.
• In vivo observations in mice confirm a similar HDL uptake pattern in endothelial cells.
• The endothelium is identified as a significant site for HDL endocytosis and transcytosis.