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 a cardiovascular disease (CVD) risk factor.
• Chylomicrons facilitate fatty acid (FA) and apolipoprotein B (apoB) transport across the arterial EC barrier.

Purpose of the Study:

• To investigate how chylomicrons impact ECs and FA transfer.
• To identify components released by ECs that affect macrophages.
• To understand the role of extracellular vesicles (EVs) in EC-macrophage interactions.

Main Methods:

• Characterization of EVs from chylomicron-treated ECs (protein, lipid, microRNA).
• Assessment of EV-induced transcriptional changes in macrophages and ECs.
• Tracking of labeled fatty acids from chylomicrons through ECs.

Main Results:

• Chylomicron treatment induced ECs to produce EVs that caused macrophage lipid droplet (LD) accumulation.
• EVs contained phospholipids and diacylglycerols; labeled FAs from chylomicron triglycerides were transferred into phospholipids within EVs.
• EVs from treated ECs were larger, more abundant, and contained specific microRNAs, increasing inflammatory gene expression in macrophages and ECs.

Conclusions:

• EC chylomicron metabolism generates EVs that enhance macrophage inflammation and LD formation.
• EVs mediate an autocrine inflammatory loop in ECs.
• ECs transfer chylomicron FAs into phospholipids within EVs, promoting vascular inflammation and lipid acquisition.