Extracellular Vesicles From Chylomicron-Treated Endothelial Cells Drive Macrophage Inflammation

Area of Science:

• Cardiovascular Biology
• Cellular Metabolism
• Lipid Transport

Background:

• Circulating lipids move into tissues and arteries via endothelial cell (EC) barriers.
• Elevated postprandial triglyceride-rich lipoproteins (TRLs) are linked to cardiovascular disease.
• Chylomicrons facilitate fatty acid transfer and lipoprotein entry into arterial walls.

Purpose of the Study:

• To investigate how chylomicrons impact ECs.
• To determine the mechanism of fatty acid transfer across the EC barrier.
• To identify components responsible for lipid droplet formation in macrophages.

Main Methods:

• Characterized extracellular vesicles (EVs) from chylomicron-treated ECs for content (protein, lipid, microRNA).
• Assessed EV-induced transcriptional changes in macrophages and ECs.
• Studied uptake and release of labeled fatty acids from chylomicrons by ECs.

Main Results:

• Chylomicron-treated ECs produced EVs that induced lipid droplet accumulation in macrophages.
• EVs contained phospholipids and diacylglycerols; chylomicron triglycerides exited ECs as phospholipids.
• EVs from treated ECs were larger, more abundant, and contained specific microRNAs, increasing inflammatory gene expression.

Conclusions:

• Endothelial cell (EC) chylomicron metabolism generates EVs that drive macrophage inflammation and lipid droplet formation.
• These EVs also promote EC inflammation, indicating an autocrine inflammatory loop.
• This process represents a key pathway for vascular inflammation and tissue lipid acquisition.