Electronegative VLDL subfraction causes endothelial damage in the metabolic syndrome
MedWire News: The negatively charged very-low-density lipoprotein (VLDL) cholesterol subfraction V5 is "highly toxic" to the vascular endothelium, report researchers.
Furthermore, the proportion of V5 in total VLDL is higher in patients with the metabolic syndrome than in normal healthy individuals, and positively correlated with levels of total cholesterol and triglycerides, they say.
"Our results strongly suggest that hypertriglyceridemia is an independent cardiac risk factor that acts, in part, via the direct endothelium-damaging effects of V5," say Chu-Huang Chen (Texas Heart Institute, Houston, Texas, USA) and co-investigators.
The researchers investigated the effects of electronegative VLDL on the vascular epithelium using plasma samples from individuals with (n=13) and without (n=13; controls) the metabolic syndrome (defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines). VLDL was separated into subfractions (V1-V5) by anion-exchange chromatography.
Compared with controls, individuals with the metabolic syndrome had a significantly higher percentage of V5 VLDL (39 vs 34%).
Moreover, the plasma concentration of V5 was 2.8-fold higher in the metabolic syndrome group than in the control group (15.2 vs 5.5 mg/dL), and correlated positively with total cholesterol and triglyceride levels.
To determine whether VLDL from individuals with the metabolic syndrome is more toxic to the endothelium than control VLDL, the researchers exposed cultured human aortic endothelial cells to 10-50 µg/mL of V1-V5 and unfractionated VLDL from the study participants.
They report that, even at low concentrations (10 µg/mL), V5 induced apoptosis in approximately 50% of endothelial cells in 24 hours.
V5 was also the most rapidly (<15 minutes) internalized subfraction, and induced the production of reactive oxygen species (ROS), notes the team.
"We present novel evidence that V5… directly damages the endothelium," say Chen et al in Diabetes Care. "The potential impact of V5-rich VLDL warrants further investigation."
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By Nikki Withers